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REVIEW

Positioning

Snezhana Oliferenko,2 Ting Gang Chew, and Mohan K. Balasubramanian1 Temasek Life Sciences Laboratory and the Department of Biological Sciences, National University of Singapore, Singapore 117604, Singapore

Cytokinesis is the terminal step of the cycle during a structure that resembles a ring or a belt in a plane which a mother cell divides into daughter cells. Often, perpendicular to the axis along which the the machinery of cytokinesis is positioned in such a way are segregated (Schroeder 1968, 1973; Fujiwara and that daughter cells are born roughly equal in size. Pollard 1976; Mabuchi and Okuno 1977; Marks et al. However, in many specialized cell types or under certain 1986; Balasubramanian et al. 1992; Bi et al. 1998). environmental conditions, the machinery is Constriction of this so-called actomyosin or contractile placed at nonmedial positions to produce daughter cells ring generates the forces necessary for the cleavage of of different sizes and in many cases of different fates. a mother cell into two daughters. Constriction of the ring Here we review the different mechanisms that position is precisely coordinated with membrane trafficking the division machinery in prokaryotic and eukaryotic events such that the new membranes and cell walls (in cell types. We also describe cytokinesis-positioning mech- fungi) are added in concert with ring constriction. In anisms that are not adequately explained by studies in nearly all , the -like FtsZ assem- model organisms and model cell types. bles into a ring structure that is perpendicular to the axis of segregation (Bi and Lutkenhaus 1991). Cytokinesis is the terminal step in the cell cycle when This so-called Z-ring is attached to the overlying plasma barriers in the form of new membranes (and cell walls in membrane via integral membrane (Hale and some cases) are generated, so as to divide a mother cell de Boer 1997; Pichoff and Lutkenhaus 2005). Although into two daughter cells. Studies of cytokinesis have molecular motors resembling the canonical eukaryotic largely focused on three major questions: (1) What is the -based motors, such as and , machinery that physically divides a cell? (2) How and have not been discovered in bacteria, the Z-ring serves to where in the cell is this machinery positioned? and (3) recruit proteins important for division septum assembly. What regulates the timing of assembly of new mem- Septum assembly then ensues in coordination with branes (and ) such that the process of cytokinesis constriction of the bacterial Z-ring. Although a contrac- does not cause inadvertent damage to the genetic mate- tile actomyosin-based apparatus has not been discovered rial? Several excellent recent reviews focus on the de- in plants, organize into two mirrored bun- scription of the machinery that various cell types use for dles that serve to recruit machinery important for assem- cytokinesis as well as the cell cycle regulation of cytoki- bly of new membranes and cell wall. These dynamic nesis (McCollum and Gould 2001; Guertin et al. 2002; microtubules interact with F- filaments to assemble Wang 2005). In this article, we will briefly introduce the the so-called phragmoplast, a structure essential for cell division machinery but will largely focus on the cytokinesis in plant cells (Gunning and Wick 1985). In mechanisms of its positioning. contrast to cytokinesis events in bacteria, yeast, fungi, and animal cells, where membranes and cell wall mate- rial are added centripetally, new membrane assembly in The cytokinetic machinery plant cells occurs by a process of centrifugal expansion In all cell types, elements of the assemble wherein the cell wall expands outward toward the cell into distinct supramolecular assemblies to facilitate cell cortex at the division site. division (Fig. 1). A summary of molecules participating in cytokinesis in various organisms is provided in Table 1. In Spatial regulation of cytokinesis animal, yeast, and fungal cells filamentous actin (F-actin), type II , and several other proteins assemble into In many cell types, and included, cytokinesis results in the formation of equally sized daugh- ter cells. However, in many instances during development (both in single and multicellular organisms), cell division [Keywords: Animal; bacteria; cleavage furrow; cytokinesis; plant; yeast; fungi] produces daughters of unequal sizes and differing fates. For Corresponding authors. example, under poor nutritional conditions, the soil bacte- 1E-MAIL [email protected]; FAX 65-6-872-7012. 2E-MAIL [email protected]; FAX 65-6872-7007. rium divides asymmetrically to produce Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1772009. a small spore, which is capable of withstanding harsher

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Positioning cytokinesis

Despite the diversity of division site-positioning mecha- nisms, it appears that in most organisms, more than one mechanism functions to ensure fidelity of division site placement. In many instances in eukaryotic cells, such fidelity is established by overlapping activatory and inhibitory mechanisms. In contrast, in prokaryotes, over- lapping negative regulatory mechanisms solely participate in division site selection, and stimulatory mechanisms have not been described. We will now describe in some detail division site placement mechanisms in various organisms.

Bacteria Bacteria exhibit a bewildering biodiversity; as a result, no bacterium in particular serves as a model to understand bacterial cell division in general. However, given the vast number of studies in the Gram-negative bacterium Escher- ichia coli and the Gram-positive bacterium B. subtilis,we focus on the mechanism of division site selection in these Figure 1. Assembly of cytoskeletal proteins into cytokinetic species. In E. coli and B. subtilis, which are cylindrical in machineries in different cell types. A contractile ring composed shape, division site selection depends on two overlapping mainly of F-actin and myosin is used for cytokinesis in animal inhibitory mechanisms (Fig. 2). The Mini-cell (Min) sys- cells and fungi. In bacteria, a tubulin-like protein FtsZ assembles into a ring-structure at the division site. Plant cells use a micro- tem (de Boer et al. 1989) prevents assembly of the Z-ring at tubule-based machinery known as the phragmoplast for cell the cell ends, while the process of occlusion division. prevents Z-ring assembly in the vicinity of the (chromosomal DNA) (Goehring and Beckwith 2005). Cy- tokinesis has also been studied extensively in Caulobacter environmental conditions. During such a sporulation crescentus, where a novel protein MipZ, unrelated to the process, B. subtilis cells ignore the medial division site Min in sequence, plays a key role in positioning the Z-ring typically chosen during vegetative growth, and instead (Thanbichler and Shapiro 2006). assemble a Z-ring at nonmedial locations in the cell. In In E. coli and B. subtilis, the key elements of the Min the budding yeast Saccharomyces cerevisiae, every cell system include two components, MinC and MinD, which division event results in the formation of a smaller and localize to the cell ends, where they prevent assembly of a larger cell, each of which inherits a different fate, with Z-rings (Marston et al. 1998; Marston and Errington 1999; the larger cell (mother cell) capable of switching its Pichoff and Lutkenhaus 2001; Lutkenhaus 2007; Dajkovic mating type, while the smaller cell (daughter cell) is et al. 2008). The spatial restriction of MinC and MinD incapable of doing so. Asymmetric cell divisions are also products to the cell poles is achieved by two un- frequently observed in metazoan cells, in which the related proteins, MinE in E. coli (Raskin and de Boer 1997, larger and smaller daughter cells inherit different fates. 1999; Fu et al. 2001; Hale et al. 2001; Shih et al. 2003) and Since asymmetric cell division events (at nonmedial DivIVA in B. subtilis (Edwards and Errington 1997; cellular locations) increase the chances of the genetic Edwards et al. 2000). In addition, in B. subtilis, the novel material being damaged by the constricting cell division protein MinJ appears to participate in linking MinCD to apparatus, such divisions are largely accompanied by DivIVA (Bramkamp et al. 2008; Patrick and Kearns 2008). mechanisms that help capture the DNA-segregating MinD is an ATPase, which in its ATP-bound form binds apparatuses in both prokaryotic and eukaryotic cells. cell membranes at the cell poles. MinD-ATP at the cell

Table 1. Protein families participating in cytokinesis Actin Myosin Tubulin Homologs Cytokinesis Homologs Cytokinesis Homologs Cytokinesis Homologs Cytokinesis Homologs Cytokinesis Animal Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Plant Yes Yes Yes No Yes Yes Yes Yes No No Yeast Yes Yes Yes Yes Yes Yesa Yes Yesb Yes Yesb Bacteria Yes (MreB) No No No Yes (FtsZ) Yes No No No No Protozoa Yes No Yes No Yes Yes Yes Yes Yes Yes aFunctions in nuclear positioning in yeast. bFunctions in mitotic spindle positioning and cytokinetic fidelity in budding yeast.

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are significantly reduced (Perry and Edwards 2004), which in turn permits Z-ring assembly in the vicinity of the cell ends. Interestingly, DivIVA, which normally functions to retain MinCD at cell ends, is retained at cell ends in the absence of MinCD. In the absence of MinCD, cell pole- localized DivIVA performs a novel second function and captures the origin of chromosome replication (OriC) by localizing a novel protein RacA to the cell poles (Thomaides et al. 2001; Wu and Errington 2003; Perry and Edwards 2004), so as to allow efficient segregation of Figure 2. Selection of the division site by two overlapping a copy of the replicated chromosome into the smaller inhibitory mechanisms in cylindrical bacteria. The Min system daughter (spore) cell. Curiously, sporulating wild-type prevents FtsZ ring assembly at the cell ends, and the nucleoid Bacillus cells, but not E. coli min-mutants, accumulate occlusion machinery prevents FtsZring assembly in the vicinity a full component of the into the smaller daughter of the nucleoids. cells. These observations might underscore the impor- tance of a mechanism that captures the DNA segregation machinery in organisms that have evolved to undergo ends recruits MinC, which prevents Z-ring assembly by asymmetric cell divisions, even in prokaryotes (Ben- its ability to bind and prevent polymerization of FtsZ (Hu Yehuda et al. 2003, 2005). Interestingly, C. crescentus, et al. 1999; Pichoff and Lutkenhaus 2001; Shiomi and which divides asymmetrically, uses a DNA-binding pro- Margolin 2007; Dajkovic et al. 2008). The boundary of the tein, ParB, to efficiently capture origins of DNA replica- MinCD-containing zone at the cell poles is established by tion to achieve proper spatial coordination of DNA MinE, a protein that has the potential to displace MinC segregation and cytokinesis (Bowman et al. 2008; Ebersbach from MinD and stimulate its ATPase activity, thereby et al. 2008). causing the release of MinD-ADP from membranes at the Although the Min system represents the primary cell poles (Hu and Lutkenhaus 1999, 2001; Suefuji et al. mechanism of division site placement in many cylindri- 2002; Hu et al. 2003; Lackner et al. 2003). Intriguingly, cal bacteria, several studies have shown that the presence MinCD is found at only one end of the cell at any given of nearby nucleoids also prevents assembly of Z-rings time in E. coli. However, the E. coli Min system exhibits (Woldringh et al. 1991; Yu and Margolin 1999; Sun and a fascinating oscillatory behavior both and in vivo Margolin 2004). Two unrelated DNA-binding proteins, (Raskin and de Boer 1999; Fu et al. 2001; Shih et al. 2003; SlmA (E. coli) (Bernhardt and de Boer 2005) and Noc Loose et al. 2008). Such oscillatory behavior in vivo leads (B. subtilis) (Wu and Errington 2004), have been shown to its association with each of the cell ends for short to represent key effectors of nucleoid occlusion. Al- periods of time, which in turn prevents Z-ring assembly though the biochemical basis of Noc function remains at both ends of the cell (Raskin and de Boer 1999; Fu et al. unknown, SlmA appears to affect Z-ring assembly by 2001; Shih et al. 2003). In contrast, the Min system does directly interacting with FtsZ (Bernhardt and de Boer not display an oscillatory behavior in B. subtilis and is 2005). It is possible that such interactions between effec- permanently associated with both cell poles by interac- tors of nucleoid occlusion and FtsZ might prevent asso- tion with the coiled-coil domain-containing protein, ciation of FtsZ-polymers with the cell membranes over DivIVA (Edwards and Errington 1997; Marston et al. nucleoids. 1998). Interestingly, although the MinCD system in B. While current studies have provided a fairly good view subtilis and E. coli acts to prevent FtsZ-ring assembly, the of mechanisms of division site placement in cylindrical B. subtilis proteins appear to prevent FtsZ-ring assembly bacteria, FtsZ- and Z-rings are also used for cell division only in the vicinity of the new cell poles created as in spherical bacteria. Although fewer studies have fo- a result of cell division (Gregory et al. 2008). The cused on spherical bacteria, it appears that Min or Min- evolutionary benefits of an oscillatory Min system over like systems might participate to detect slight alterations a Min system anchored to both cell poles are not un- in spherical morphology (Huang and Wingreen 2004), derstood. thereby determining a long DNA segregation axis, per- Studies in B. subtilis have shown that the establish- pendicular to which the Z-ring could be assembled. A ment and maintenance of the position of the division site canonical Min system has been described in Neisseria is a continuous process. Upon transfer to poorer nutri- and Deinococcus (White et al. 1999; Ramirez-Arcos et al. tional conditions, B. subtilis cells undergo a developmental 2001). Furthermore, Min-proteins have been shown to program in which a mother cell divides asymmetrically undergo oscillations in random orientations in spherical to produce a smaller spore. Time-lapse studies of sporu- mutant cells of E. coli (Corbin et al. 2002). Although lating cells have shown that medially organized Z-rings, MinC- and MinD-like proteins have not been identified assembled during vegetative growth, unravel into spirals in Staphylococcus and Streptococcus, as-yet-unidentified that eventually accumulate and organize Z-rings at both functional homologs of the Min system might exist in ends of the cell, although only one of these matures, and these bacteria. It is therefore likely that Z-ring positioning only one spore is generated (Ben-Yehuda and Losick in spherical bacteria might also be under negative regu- 2002). Under conditions of sporulation, levels of MinCD lation by Min and Min-like proteins. Although relatively

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Positioning cytokinesis unexplored, nucleoid occlusion might also participate in either proximal or distal to the site of previous cell Z-ring positioning in spherical bacteria. division (Fig. 3; Chant and Herskowitz 1991; Chant 1999; Casamayor and Snyder 2002). Cytokinesis and cell Eukaryotic cells division are achieved by the cleavage of the neck region of budding yeast cells (Fig. 3). Interestingly, since the site of Division site positioning in eukaryotes utilizes diverse cell polarization, which is established early in the cell machinery and is established at different points in the cell cycle, dictates the site of cytokinesis, the mitotic appa- cycle in different organisms. For example, the site of cell ratus does not play any appreciable role in the positioning division is selected in interphase in the yeasts S. cerevisiae of the division site in this organism, but instead functions (in G1) and Schizosaccharomyces pombe (in G2). In later to ensure correct positioning of daughter contrast, the site of cell division is chosen during mitosis with respect to the division site. (in late anaphase and/or telophase) in animal cells. Finally, The site of bud assembly is marked by landmark the site of cell division is chosen early in mitosis (in proteins such as Bud3p, Bud4p, Bud10p, and Axl1p in prometaphase) in plant cells. Furthermore, cell division the case of axial budding (Chant 1999; Casamayor and generates daughters of equal size in some organisms and Snyder 2002), and Bud8p and Bud9p in the case of bipolar cell types, whereas in other organisms and cell types, this budding (Fig. 4; Harkins et al. 2001). These landmark process generates daughters of differing sizes and fates. proteins help recruit the Ras-related GTPase, Rsr1p/ This diversity of cell cycle and spatial regulation has led to Bud1p (Bender and Pringle 1989). Rsr1p/Bud1p, in turn, the evolution of several mechanisms that participate in the recruits the exchange factor for the Cdc42p-GTPase, establishment of the site of cell division in eukaryotic cells. Cdc24p, leading to the localized activation of the Cdc42p (Park et al. 1997). GTP-bound Cdc42p then recruits the Mitotic apparatus-independent positioning CRIB domain-containing proteins Gic1p and Gic2p, ulti- of cytokinesis mately leading to the assembly of at the future cell division site (Iwase et al. 2006). Septins, in turn, serve Budding yeast S. cerevisiae to recruit the bud-site marker proteins to the region adjacent to the division site. Rga1p, a GTPase-activating S. cerevisiae cells grow and divide using a process of protein for Cdc42p, localizes to the division site so as to budding. At G1/S, cells assemble cortical landmark ensure that a previously used division site is not reused proteins, which recruit the growth machinery composed for polarized growth and cell division (Tong et al. 2007). of, among others, the Cdc42 GTPase, proteins required Since the cell division site is chosen early in the cell for the assembly of F-actin patches, and the machinery cycle, and since cells do not have a default axis to allow targeting secretion to this incipient site from which maximal elongation of the mitotic spindle, budding yeast growth via a bud would occur. The position of the cortical cells possess a robust mechanism that captures the landmark assembly depends on the mating type of the mitotic spindle, thereby allowing migration of one of cells. Cells of the mating types a or a, which are typically the daughter nuclei into the bud. This spindle capture is haploid, grow by the assembly of buds at axial locations achieved by the localization of Kar9p and a dynein, that are positioned adjacent to the site of the previous Dyn1p, to one of the spindle pole bodies and asters, causing division in both the daughter cells (Fig. 3). In contrast, a type V myosin-dependent movement of the SPB/aster cells of the mating types a/a, which are typically diploid, containing Kar9p and Dyn1p into the bud (Yeh et al. 2000; grow by assembly of buds at bipolar locations, which are Schuyler and Pellman 2001; Liakopoulos et al. 2003; Sheeman et al. 2003). Failure to orient the spindle along the mother–bud axis delays activation of the Mitotic Exit Network (MEN), which is essential for cytokinesis, until proper orientation of the spindle is achieved (Fig. 5; Schuyler and Pellman 2001).

The fission yeast S. pombe Cells of S. pombe are cylindrically shaped and divide by placement of an and a division septum that divides a mother cell into two roughly equally sized cells. The division site placement principally depends on the position of the premitotic nucleus (Paoletti and Chang 2000). The division site in fission yeast is chosen in late G2 phase and is dynamic, in that alterations in the position of Figure 3. Different budding patterns in haploid and diploid S. cerevisiae. Haploid cells use Bud3p, Bud4p, Axl1p, and Axl2p as the nucleus until early mitosis cause repositioning of the the landmarks to position the bud site at axial locations. cell division site as well (Daga and Chang 2005; Tolic- Diploid cells select the bud site using Bud8p and Bud9p as Nørrelykke et al. 2005). landmarks and undergo bipolar budding either at proximal or Division site selection in fission yeast involves interplay distal locations. between two physical parameters: the cylindrical cell

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(Fig. 6; Sohrmann et al. 1996; Paoletti and Chang 2000). Mid1p is a membrane-associated protein related to meta- zoan anillins in terms of domain organization. Mid1p shuttles between the nucleus and the cell cortex, local- izing to the nucleus during most of interphase and to the overlying cortex in late G2 and early mitosis (Paoletti and Chang 2000). Mid1p recruits several components of the actomyosin ring to the medial region of the cell so as to allow actomyosin ring assembly overlying the position of the interphase nucleus (Motegi et al. 2004). Mid1p is exported from the nucleus upon entry into mitosis by phosphorylation by the Polo-family protein kinase, Plo1p (Bahler et al. 1998). Consequently, plo1 mutants also are defective in division site placement (Bahler et al. 1998). The polarity factors Tea1p, Pom1p, and Tea4p, which localize to the cell ends, prevent accumulation of Mid1p at one of the cell ends (the new end, which is generated following cell division) (Celton-Morizur et al. 2006; Padte et al. 2006). How Mid1p is excluded from the other (older) end remains unknown. Cells lacking Mid1p, despite the mispositioning of the division septum, do not assemble septa at the ends of the cell (Huang et al. 2007). In- Figure 4. Positioning of the division site in the budding yeast. terestingly, this ‘‘tip occlusion’’ of septation is also achieved A zone of inhibition is established by the Cdc42p GTPase via Tea1p, Tea4p, and Pom1p. It appears that Tea1p, activating protein Rga1p at the previous bud site. The landmark Tea4p, and Pom1p delay septum assembly, by down- proteins are then recruited to the presumptive bud site. These regulating function of the F-BAR protein Cdc15p, until landmark proteins help to recruit a Ras-related protein, Rsr1p, actomyosin rings misplaced in the absence of Mid1p exit which leads to the recruitment of Cdc42p GEF Cdc24p, causing the cell ends (Huang et al. 2007). It is likely that such local activation of Cdc42p. The activated Cdc42p then recruits a mechanism might contribute to the fidelity of cytoki- the CRIB domain-containing proteins, Gic1p and Gic2p, and nesis in smaller cells, where the ends are nearer to the leads to the assembly of septins at the division site. Septins, in mid-cell site. The protein kinase Kin1p has also been turn, promote actomyosin ring assembly at the division site. Rga1p then localizes to the division site to ensure that a pre- shown to participate in division placement, although viously used division site is not reused for polarized growth and mechanistic details are presently unknown (La Carbona cell division. and Le Goff 2006).

Templated cytokinesis along cellular long axis morphology and the medially positioned nucleus (Sipiczki in Trypanosoma brucei et al. 2000; Daga and Chang 2005; Ge et al. 2005). The anillin-related protein, Mid1p, stimulates actomyosin ring The African protozoan T. brucei has a highly organized assembly at the cortex overlying the nucleus (Motegi et al. and polarized cellular structure. It contains a single Golgi 2004), while a host of so-called tip factors simultaneously body and a single , which are located at inhibit cytokinesis at cell ends (Celton-Morizur et al. 2006; specific intracellular positions. Correct positioning of Padte et al. 2006; Huang et al. 2007). The cylindrical shape the division machinery is thus crucial for the faithful of fission yeast cells is established by F-actin-dependent inheritance of a nucleus and one each of these organ- assembly of cell wall components. Elements of the F-actin elles. Curiously, there is no evidence at present for the cytoskeleton, Cdc42-GTPase, and the machinery involved in a-glucan and b-glucan synthesis, are all important for the establishment and maintenance of cylindrical cellular shape (Diaz et al. 1993; Miller and Johnson 1994; Verde et al. 1998). The cylindrical shape of the cell allows spontaneous organization of anti-parallel bundles of microtubules, with a region of overlap of minus ends in the medial region of the cell (Carazo-Salas and Nurse 2006; Daga et al. 2006; Terenna et al. 2008). Since these regions Figure 5. Coordination of spindle orientation and cytokinesis of overlap are mostly associated with the , by the MEN in budding yeast. A GTPase-driven signaling spontaneous organization of microtubules within the pathway, MEN is kept inactive when the mitotic spindle is confines of a cylindrical shape ensures medial positioning not positioned at the neck region connecting the mother and of the nucleus (Tran et al. 2001). daughter cells. Once the mitotic spindle is aligned along the The positioning of the nucleus dictates the site of cell mother and bud axis, MEN is activated to promote mitotic exit division via the PH domain-containing protein Mid1p and cytokinesis.

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Positioning cytokinesis

other Trypanosomal species as well as in other organisms such as Leishmania major, although mechanisms un- derlying division site placement in these organisms are not well understood.

Establishment of the division plane in plant cells Plant cells are encased by cell wall material and, unlike animal cells, are unable to migrate. Thus, proper organi- zation of pattern and morphology of plant tissues depends largely on the precise positioning of the division plane. Improper specification of the division plane in plant cells results in missegregation of cell fate determinants and defective tissue morphology and patterning. In contrast to animal cells that use an actomyosin- based contractile ring for cytokinesis, plant cells mainly use microtubule-based structures for cell division. In Figure 6. Division site selection in the fission yeast S. pombe. addition to the mitotic spindle, two additional microtu- The division site is determined by the position of the premitotic bule-based cellular structures known as the preprophase nucleus in fission yeast through Mid1p, an anillin-related pro- band (PPB) and phragmoplast play crucial roles in plant tein. Mid1p shuttles between nucleus and cell cortex during cytokinesis (Gunning and Wick 1985). PPB is a ring-like interphase. Upon entry into mitosis, Polo-related kinase Plo1p structure composed of microtubules and F-actin that is promotes the exit of Mid1p from the nucleus to specify the positioned underneath plasma membrane and circum- division zone. The cortically localized Mid1p then promotes scribes the premitotic nucleus. In contrast, the phragmo- assembly of the actomyosin ring at the division site. During plast is a structure assembled during cytokinesis that cytokinesis, a tip complex prevents septum assembly at the cell consists of two parallel microtubule bundles separated by ends. the expanding cell plate in the middle. In most plant cell types, an array of parallel microtu- bule bundles oriented perpendicular to the cell’s long axis existence of an actomyosin-based cytokinetic apparatus is organized underlying the cell cortex during interphase in T. brucei. (Fig. 8). This cortical microtubular array contributes in In T. brucei, a single is attached to the cell interphase to the formation of PPB, whose position body via the flagellum attachment zone (FAZ) (Kohl et al. corresponds to that of the future division site (Hardham 1999). During cell cycle progression, the old flagellum and Gunning 1978; Mineyuki et al. 1999). Thus, similar guides the growth of a new flagellum along the length of to yeast cells, plant cells specify their division plane the cell body (Moreira-Leite et al. 2001). After mitosis, before entering mitosis. As the cell cycle proceeds, the a cleavage furrow is formed between these flagella, and the furrow ingresses unidirectionally along the long axis, initiating at the anterior and ending at the posterior side (Kohl et al. 1999). The distal tip of the new flagellum (and its associated FAZ) promotes cytokinesis from the ante- rior end of the cell (Fig. 7; Vaughan and Gull 2003). T. brucei mutants that are defective in intraflagellum trans- port (IFT) have a shorter new flagellum and, interestingly, undergo unequal cell division (Kohl et al. 2003). Thus, the length of the flagellum of T. brucei increases by IFT and the flagellar length affect the position of cleavage furrow. Procyclic cells of T. brucei in the tsetse fly midgut undergo a few rounds of symmetrical cell division and then differentiate into an epimastigote form while mi- grating toward the salivary glands (Sharma et al. 2008). This differentiation process also involves an asymmetric cell division in which a long cell and a short epimastigote cell are produced. The procyclic T. brucei increases its cell body length to almost double its original length prior to the asymmetric cell division, and a short new flagel- Figure 7. Cytokinesis in the African protozoan T. brucei. T. lum is grown from the posterior end (Sharma et al. 2008). brucei duplicates its such as the nucleus and the Ingression of the cleavage furrow from the distal tip of the flagellum during mitosis. After completion of mitosis, cytoki- short new flagellum leads to the production of two nesis is initiated from the anterior end to the posterior end. The daughter cells with different cell sizes (Sharma et al. cleavage furrow ingresses unidirectionally from the distal tip of 2008). Division along the long axis is also observed in the flagellum.

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et al. 2007). Once localized to the cortex, TANGLED persists after the PPB is disassembled and remains at the future division site in a microtubule-independent manner (Walker et al. 2007). It then guides the expanding phrag- moplast to the cortical area previously occupied by PPB during cytokinesis. How TANGLED guides the phragmo- plast expansion toward the PPB-marked cortex remains unclear. It has been hypothesized that TANGLED resem- bles vertebrate adenomatous polyposis coli (APC) pro- Figure 8. Establishment of the division plane in plant cells. teins and might potentially interact with EB1 at the plus Microtubule bundles underlying cell cortex are oriented perpen- ends of microtubules radiating from the phragmoplast. dicular to the cell’s long axis during interphase. The microtu- Future studies should identify the precise mechanisms by bule array condenses, and a PPB is formed underneath plasma membrane, whose position predicts the future division site. which TANGLED and related proteins function. Never- Upon entry into mitosis, the PPB is disassembled, and F-actin is theless, the presence of TANGLED protein in both depleted from the cortical region occupied by the PPB. Land- monocots and dicots suggests that a conserved mecha- mark proteins such as TANGLED remain at the PPB to mark the nism might specify the division zone in plants. division site. After mitosis, a microtubule-based structure, termed the phragmoplast, is formed and expands laterally to- Mitotic apparatus-dependent division site positioning ward the cell cortex region occupied by the PPB. Targeted in animal cells vesicular trafficking and fusion at the phragmoplast lead to the assembly of cell wall at the division site. Cytokinesis in animal cells is achieved by constriction of the cortex between the two sets of segregated chromo- parallel cortical microtubular array condenses at the cell somes. Many models have been suggested over the years cortex overlying the premitotic nucleus. Several studies to explain how cortical activity could be regulated: An have suggested that the nuclear position determines the excellent historical overview of cytokinesis studies in position of PPB and the future division site (Murata and 19th and 20th centuries can be found in Rappaport (1986). Wada 1991; Gimenez-Abian et al. 2004). Displacement It was eventually established that cytokinesis is initiated of the interphase nucleus triggers the establishment of by signal(s) emitted from the mitotic apparatus. When the the PPB and the division site close to the new nuclear mitotic spindle in starfish eggs was pushed or rotated, the position (Murata and Wada 1991). Upon entry into cortical contractile ring was assembled at a new position, mitosis, the PPB disassembles, and F-actin is depleted corresponding to that of the spindle (Rappaport and from the cortical region occupied by the PPB (Cleary Ebstein 1965; Rappaport and Rappaport 1993). These 1992, 1995; Liu and Palevitz 1992). It has been proposed experiments demonstrated that the cortex of the echino- that the loss of microtubules and F-actin from the PPB derm eggs is initially capable of furrowing at any location, leads to the accumulation of a landmark protein to mark but the orientation and position of the spindle determine the future division site. After , the actual division plane. Therefore, the current view is the remnants of the anaphase spindle form the phragmo- that microtubules associated with the spindle apparatus plast, which then expands laterally toward the cortical play a crucial role in controlling furrow positioning and area occupied by the PPB. Vesicular trafficking and ingression. During anaphase, the mitotic spindle in most fusion, targeted by microtubule bundles at the edge of animal cells contains a set of bundled microtubules phragmoplast, lead to the formation of cell plate. After (central spindle) and two radial arrays of astral micro- completion of cytokinesis, the microtubule bundles reor- tubules. Each of these arrays differentially controls acto- ient their position to reform the parallel cortical micro- myosin cortical activity and can induce furrow formation tubular array in the two newly separated daughter cells. (Fig. 9). However, they often cooperate to induce furrow- The question of how the PPB defines the future division ing specifically between separated chromosomes. The plane had been a puzzle for decades. Characterization of exact contributions of these various microtubular arrays a novel protein, TANGLED, in maize and its homolog in differ among cell types. Arabidopsis has led to the suggestion that this protein Regulation by astral microtubules might function as the long-sought landmark protein that marks the division plane after PPB disassembly (Smith It appears that in cells that have large asters, the astral et al. 1996; Walker et al. 2007). Maize mutants defective microtubules play an important role in the determination in TANGLED function have a misoriented division plane, of the cleavage plane. It has been proposed that astral as the phragmoplast is not guided toward the cortex microtubules may provide inhibitory signals to the polar defined by PPB (Cleary and Smith 1998). A similar but cortical regions, resulting in local inhibition of contrac- weaker phenotype has been observed in the Arabidopsis tility and establishment of the gradient of cortical ten- tan mutant, in which a population of root-tip cells display sion. In such a manner, the highest tension and cortical tilted division planes that are unable to form a cell plate furrowing would be then restricted to cell equator (Wolpert perpendicular to cell’s long axis. Arabidopsis TANGLED 1960; White and Borisy 1983). These models are cumula- is recruited by microtubules and kinesins to the cortical tively known as polar relaxation models. Consistently, region occupied by the PPB during interphase (Walker a complete lack of microtubules leads to the enhanced,

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Bonaccorsi et al. 1998; Mishima et al. 2002, 2004). Thus, if the spindle is off-center, the division is asymmetric with the mother cell giving rise to two daughters of different sizes. However, in situations in which spindles do not have asters, like in oocytes during female meiosis in the mouse (Szollosi et al. 1972), the cleavage furrow position is controlled solely by the central spindle.

Transmission of the furrow positioning signals from microtubule arrays to cell cortex It appears that microtubules of the spindle apparatus control cortical contractility largely by maintaining ac- tive gradients of the small GTPase Rho through the Figure 9. Three models for cleavage plane positioning in positioning of Rho regulators on microtubules. Rho is animal cells. Three modes of division site positioning have been a critical regulator of cleavage furrow induction, and its demonstrated in animal cells. After chromosome segregation, activity is required for cortex furrowing, as first shown by the overlapping microtubule bundles at the cell midzone known Mabuchi et al. (1993), Kishi et al. (1993), and Drechsel as the central spindle specify the cleavage plane. In certain cell et al. (1997). Similar to its function in other actomyosin- types, astral microtubules stimulate cleavage furrow formation dependent processes, active GTP-bound Rho induces at the division site, whereas in some cases, astral microtubules F-actin assembly (Watanabe et al. 1997) and causes inhibit cortical contractility at the cell ends to promote cleavage activation of myosin II function (Kimura et al. 1996) at furrow formation at the division site. the cell equator, thereby promoting cortical constriction. Active Rho accumulates in a narrow cortical band overlying the mitotic spindle, and spindle displacement although disorganized, cortical contractility (Canman leads to repositioning of this cortical band of active Rho et al. 2000; Paluch et al. 2005). (Bement et al. 2005). Activities of Rho guanine nucleotide On the other hand, classic experiments of Rappaport on exchange factor (GEF), ECT2, and a proposed Rho GAP shaping the sand dollar eggs into toruses suggested that it (GTPase-activating protein), Cyk4, are needed to sustain is the equatorial zone where microtubule asters converge Rho function in cytokinesis (for review, see Piekny et al. at the cortex that determines position of the cleavage 2005). A traditional view is that ECT2 function is initially furrow (Rappaport 1961). Theories that propose that required for the accumulation of GTP-bound Rho at the a subpopulation of mitotic asters stimulate the future cell equator, in order to promote furrowing while down- furrow region, possibly through delivery of a factor that regulation of Rho through the GAP activity induces could be transported along microtubules, are known as disassembly of the cytokinetic machinery and promotes astral stimulation models. In such models, activity of the completion of cytokinesis (Minoshima et al. 2003). In this proposed furrowing activator would be highest at the manner, it is assumed that activation of Rho and its down- equatorial cortex, where asters from two spindle poles regulation happen sequentially, driven by cell cycle cues. meet. Astral stimulation has been proposed for position- Recently it was reported that the GAP activity is, in fact, ing of furrows in large cells (fertilized eggs of amphibians, required throughout cytokinesis in Xenopus embryos, birds, and fish) and in cells with several mitotic appara- even at its early stages, to form and maintain the narrow tuses (insects). Mathematical modeling of astral stimula- Rho activity zone at the cell equator. When the GAP was tion correctly predicts the positioning and occurrence of inactivated, Rho activity zones were poorly focused and furrowing when cell shape is significantly altered before exhibited unstable and often oscillatory behavior early division (Devore et al. 1989). during cytokinesis, presumably triggering cytokinesis fail- ures (Miller and Bement 2009). Thus it appears that Rho Regulation by the spindle midzone activity zones represent not simply the zones of local Cytokinetic positioning and furrowing also appear to be activation but zones where Rho undergoes fast GTPase influenced by proteins residing at the spindle midzone in ‘‘flux.’’ Consistent with this notion, Aurora kinase that some cell types. The role of the spindle midzone in phosphorylates Cyk4 (which otherwise exhibits a Rac determining the cleavage position was first determined GAP activity) and triggers its conversion into a Rho GAP in the studies of unequal cell division in grasshopper (Minoshima et al. 2003) produces a phosphorylation gra- neuroblasts. Unequally sized asters determined the asym- dient that extends from the spindle midzone to the cortex metric positioning of the spindle, but it was the cell immediately after anaphase onset (Fuller et al. 2008). Thus cortex nearest the spindle midzone that received cleavage it appears that the machinery is in place to enable rapid stimulus. Furthermore, furrowing required the continu- GTPase cycles of Rho precisely at the cell equator. This ous stimulation from the spindle midzone (Kawamura might provide a part of the answer to an interesting 1977). Many studies have shown that the central spindle question as to how exactly the furrowing signals are trans- together with asters are involved in the positioning of the mitted from the spindle midzone to the equatorial cortex, cleavage furrow (Rappaport 1985; Cao and Wang 1996; frequently on micrometer scale distances. Cytokinetic

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Oliferenko et al. regulators, such as the Aurora B–Incenp–Survivin com- allows daughter cells to adopt distinct fates. In multicel- plex and the central spindlin complex consisting of the lular organisms, a rather simple, ‘‘symmetric’’ cell di- kinesin-like protein MKLP1 and Cyk4, all localize to the vision (when a mother cell divides into approximately spindle midzone during anaphase. The Aurora kinase equally sized daughters bearing same cellular fates) is complex is required for central spindlin localization and often oriented, and such orientation is essential to sustain function (Severson et al. 2000), but it is also possible that a specific tissue shape and function. For instance, in it may have other targets. Furthermore, control of Rho animal epithelium, the dividing cells remain in contact activity at the cleavage furrow is not limited to regula- with and with each other, and tion by Aurora kinase. The polo-like kinase 1, Plk1, thereby maintain the sheet-like structure of this tissue. promotes recruitment of the Rho GEF, ECT2, to the Cell division can also result in asymmetric segregation of central spindle, independently of Aurora B (Petronczki factors leading daughter cells to take on different fates. et al. 2007). Plk1 in mammalian cells localizes to the Such ‘‘asymmetric’’ division is widespread in nature: central spindle through its interaction with the micro- Unicellular organisms such as budding yeast use it to tubule bundler PRC1 (Neef et al. 2007), which in turn restrict damaged and oxidized proteins to the aging interacts with several mitotic kinesins, including mother cell (Aguilaniu et al. 2003), while in complex MKLP1-like proteins, and is important for cytokinesis multicellular organisms, asymmetric division site place- (Jiang et al. 1998; Kurasawa et al. 2004; Verni et al. 2004). ment sets specific cellular patterns that contribute to Plk 1 has also been copurified with MKLP1 and has been organism development and tissue homeostasis. shown to directly phosphorylate the MKLP1 (Lee et al. As spindle orientation in animal cells sets the plane of 1995; Liu et al. 2004). Thus it appears that an interwoven future cell division, much work in recent years has also network of proteins at the spindle midzone contributes been dedicated to elucidating mechanisms underlying to regulating Rho activity at the future division site. spindle orientation both in two- and three-dimensional It is obvious from the experiments discussed above that cell cultures and in the context of a tissue (for reviews, see microtubules have been proposed to provide both stimu- Ahringer 2003; Gonzalez 2007). We will discuss them latory and inhibitory effects on cortical stiffness and only briefly. When mammalian epithelial NRK cells are contraction. Indeed, it appears that the mitotic apparatus grown as two-dimensional cultures, they remain non- is indeed capable of providing two furrow-specifying polarized. During division their spindles appear to be signals (Dechant and Glotzer 2003; Bringmann and Hyman oriented along the long axis of the cell (O’Connell and 2005). How could this be achieved? An interesting view is Wang 2000). A simple and appealing explanation is that that the key parameters positively or negatively influenc- the mitotic spindle naturally aligns with the cell’s long ing the cortical contractility are stability and possibly the axis due to geometric constraints and that this position- configuration of microtubule arrays. While a subpopula- ing ensures that the cell divides along the short axis. tion of dynamic astral microtubules seems to cause polar However, it appears that when cells are grown on the relaxation, other, more stable microtubules (which could micro-patterned substrates that provide defined contacts be stable astral or central spindle microtubules) stimulate between cell and extracellular matrix (ECM), spindle contractility at the sites where they contact the cortex orientation is driven not simply by cell geometry but (Canman et al. 2003; Chen et al. 2008; Foe and von Dassow rather by cortical marks associated with so-called re- 2008; Murthy and Wadsworth 2008). Odell and Foe re- traction fibers that are left during mitotic cell rounding. cently proposed a model wherein the dynamics of the Such cortical marks are rich in various cytoskeletal central spindlin component kinesin MKLP1 are used to proteins and reflect the status of cell/ECM contacts prior provide an explanation of how the differential microtubule to division (Thery et al. 2005, 2007). Therefore, the stability could modulate cortical contractility. In their mitotic spindle is actively oriented with respect to cell/ model, most MKLP1 is sequestered by a multitude of ECM adhesion plane or cell shape even in cells that grow dynamic astral microtubules and does not reach the cell out of the tissue context and are considered ‘‘nonpolar- cortex. Therefore, Rho activation is suppressed where ized.’’ Contributions of cell shape and cell/ECM contacts density of such microtubules is high. On the other hand, in spindle orientation in vivo are probably not mutually MKLP could be delivered to cell cortex along a subset of exclusive (and these factors might be very well be in- stable microtubules and cause Rho activation specifically terdependent), and both mechanisms could function at the cell equator (Odell and Foe 2008). This interesting depending on a physiological context. model can indeed explain how microtubules of the spindle When epithelial cells are grown on permeable matrix apparatus are capable of delivering both stimulatory and support, they form a sheet-like cellular monolayer that inhibitory signals to the cortex, depending on their stabil- exhibits many properties of true epithelium. To sustain ity and configuration. this organization through cellular expansion, a dividing cell has to ensure that it remains in contact with surrounding cells and with the matrix throughout furrow Setting up the division site in animal cells growing in the ingression. It is therefore not surprising that most spin- context of a tissue and the role of mitotic spindle dles in polarized MDCK cells are oriented perpendicular orientation to the long, apical–basal, axis of the cell, allowing cell The purpose of cytokinesis is not limited to an increase in cleavage to occur in the plane of the epithelium (Reinsch cell number. It also shapes tissues and organisms and and Karsenti 1994). Similarly, in the dorsal epiblast of the

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Positioning cytokinesis zebrafish embryo, most spindles are oriented perpendic- ular to the long axis of the cell, resulting in cellular division along the long axis. Again, such alignment suggests the existence of a mechanism actively driving spindle orientation. In epithelia, adherens junctions are located at lateral cell borders near the apical surface and contain polarity determinants and microtubule-binding proteins. Junctional complexes appear to capture astral microtubules, and forces generated by dynein could rotate spindles into alignment. Therefore, adherens junc- tions could provide the link between cell polarity and spindle orientation (Lu et al. 2001). Mutations that disrupt spindle–cortex interactions can induce abnormal divisions and contribute to hyperproliferation of daughter cells (Yamashita et al. 2003, 2007; Yamashita and Fuller Figure 10. Cytokinesis along the cellular long axis in polarized 2005, 2008). In the zebrafish embryo, injection of dominant- intestinal epithelial cells. In most cultured cell lines, the di- vision plane is positioned perpendicular to the cell’s long axis. In negative Dishevelled or down-regulation of Wnt pathway vivo, the polarized intestinal epithelial cells, however, divide components (Wnt11 and Stbm) causes randomization of along the cell’s long axis. division orientation, implicating noncanonical Wnt sig- naling pathway in controlling this process (Gong et al. 2004). Thus, the axis of division may be defined by Fleming et al. 2007). Furthermore, spindle remnants and mitotic spindle orientation that in turn is driven by midbodies were always seen at the apical cell borders and cell–cell signaling and apical–basal polarity cues (see also never at the basal or lateral borders in late telophase cells, Schlesinger et al. 1999; Schober et al. 1999; Petronczki suggesting that furrow ingression proceeds in asymmetric and Knoblich 2001 and others). fashion starting at the basal side and ending at the apical surface (Das et al. 2003; Royou et al. 2004; Fleming et al. 2007). So how could the spindle apparatus direct furrow Cell division in animal tissues: further questions ingression? Is furrowing initiated basolaterally by un- and challenges known mechanisms and then sustained through inter- Orientation of cell division in tissues can be specifically actions with spindle and astral microtubules? In this regulated in space and time to achieve the right balance of light, it might be useful to recall the polar relaxation cell expansion and cell differentiation. For instance, in model, wherein relaxation of part of the cortex allows mouse embryonic skin, some cells eventually start di- furrow ingression to occur. It would be interesting to viding perpendicular to the basement membrane, yield- evaluate whether such a mechanism could function in ing two daughters, one of which remains in the plane of the confines of the epithelial cell geometry. It might also the initial cell layer and the other becomes a so-called be possible that other factors, such as local activation of suprabasal cell. The number of such cells increases as actin depolymerization or loss of actin cytoskeleton skin stratification proceeds. When divisions proceed cross-linking, could result in a similar functional out- laterally to the basement membrane, skin stratification come. For instance, it has been shown that depletion of does not occur. Again, it appears that the plane of cell the actin cross-linking protein a- leads to a highly division is primarily determined by spindle orientation, unstable cortex and asymmetric furrow ingression which requires function of the Pins homolog LGN and (Mukhina et al. 2007). Imaging of cytokinesis in intact the inscuteable homolog mInsc. While LGN and mInsc tissues and three-dimensional cell culture models, to- constitute the cell polarity cues, p150glued, a subunit of gether with experimental perturbations of specific pro- dynein– complex, seems to function together tein function should provide insights on whether this or with the spindle pole-anchoring protein NUMA to create similar mechanisms could indeed operate. pulling forces that could position the spindle (Lechler and Fuchs 2005). It would be of great interest to continue Concluding remarks investigating the processes of spindle alignment and division site positioning in mouse animal models, look- Cytokinesis positioning mechanisms are very diverse in ing at cell division in the tissue context. Yet, results of nature, even among closely related species. For example, gene deletions and other gene manipulations could be whereas entry into and progression through S phase and notoriously difficult to interpret because of tight feedback mitosis are regulated by highly conserved mechanisms in between planar polarity and spindle orientation. all eukaryotes, the mechanisms regulating division site Curiously, it was observed that during cytokinesis in positioning are tailor-made to suit the morphology and polarized epithelial cells of mouse gastral crypts, spindles function of various cell types, some of which depend on are oriented parallel to the tissue and close to the apical the mitotic apparatus, while others do not. Similarly, surface, but furrow ingression starts from the basolateral molecules with highly divergent properties regulate cy- surface and, in fact, far away from either midspindle or tokinesis positioning even within cylindrically shaped astral microtubules (Fig. 10; Bjerknes and Cheng. 1989; bacteria. Furthermore, although division along the shortest

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Oliferenko et al. cellular axis is typically observed in prokaryotes and Bi, E.F. and Lutkenhaus, J. 1991. FtsZ ring structure associated many eukaryotes, cells of some unicellular organisms with division in . Nature 354: 161–164. and cells within the confines of the tissue also divide Bi, E., Maddox, P., Lew, D.J., Salmon, E.D., McMillan, J.N., Yeh, along the long axis of cells. Although the machinery for E., and Pringle, J.R. 1998. Involvement of an actomyosin contractile ring in Saccharomyces cerevisiae cytokinesis. J. cell division exhibits some conservation, cells use a mix- Cell Biol. 142: 1301–1312. and-match of stimulatory mechanisms that help position Bjerknes, M. and Cheng, H. 1989. Mitotic orientation in three the division site and inhibitory mechanisms that help dimensions determined from multiple projections. Biophys. avoid incorrect locations to position the site of cytoki- J. 55: 1011–1015. nesis. In some instances, despite the lack of conservation Bonaccorsi, S., Giansanti, M.G., and Gatti, M. 1998. Spindle self- of molecular components, cells appear to use similar organization and cytokinesis during male meiosis in asterless overlapping mechanisms. For example, animal cells and mutants of Drosophila melanogaster. J. Cell Biol. 142: 751– fission yeast ensure positioning of the division site by 761. stimulating equatorial actomyosin assembly as well as Bowman, G.R., Comolli, L.R., Zhu, J., Eckart, M., Koenig, M., preventing division at incorrect locations. Thus, while Downing, K.H., Moerner, W.E., Earnest, T., and Shapiro, L. 2008. A polymeric protein anchors the chromosomal origin/ some aspects of the regulation of positioning cytokinesis ParB complex at a bacterial cell pole. Cell 134: 945–955. have emerged from studies in model organisms and Bramkamp, M., Emmins, R., Weston, L., Donovan, C., Daniel, systems, understanding the mechanisms operating in R.A., and Errington, J. 2008. A novel component of the a variety of intact tissues represents a major challenge. division-site selection system of Bacillus subtilis and a new mode of action for the division inhibitor MinCD. Mol. Acknowledgments Microbiol. 70: 1556–1569. Bringmann, H. and Hyman, A.A. 2005. A cytokinesis furrow is We thank all members of the Balasubramanian and Oliferenko positioned by two consecutive signals. Nature 436: 731–734. laboratories for discussion, and Wanzhong Ge, Ramanujam Canman, J.C., Hoffman, D.B., and Salmon, E.D. 2000. The role of Srinivasan, Meredith Calvert, and Mithilesh Mishra for critical pre- and post-anaphase microtubules in the cytokinesis reading of the manuscript. Work in the laboratories of M.K.B. and phase of the cell cycle. Curr. Biol. 10: 611–614. S.O. is supported by research funds from Singapore Millennium Canman, J.C., Cameron, L.A., Maddox, P.S., Straight, A., Tirnauer, Foundation and the Temasek Life Sciences Laboratory. J.S., Mitchison, T.J., Fang, G., Kapoor, T.M., and Salmon, E.D. 2003. Determining the position of the cell division plane. References Nature 424: 1074–1078. Cao, L.G. and Wang, Y.L. 1996. Signals from the spindle Aguilaniu, H., Gustafsson, L., Rigoulet, M., and Nystrom, T. midzone are required for the stimulation of cytokinesis in 2003. Asymmetric inheritance of oxidatively damaged pro- cultured epithelial cells. Mol. Biol. Cell 7: 225–232. teins during cytokinesis. Science 299: 1751–1753. Carazo-Salas, R.E. and Nurse, P. 2006. Self-organization of Ahringer, J. 2003. Control of cell polarity and mitotic spindle interphase microtubule arrays in fission yeast. Nat. Cell positioning in animal cells. Curr. Opin. Cell Biol. 15: 73–81. Biol. 8: 1102–1107. Bahler, J., Steever, A.B., Wheatley, S., Wang, Y., Pringle, J.R., Casamayor, A. and Snyder, M. 2002. Bud-site selection and cell Gould, K.L., and McCollum, D. 1998. Role of polo kinase and polarity in budding yeast. Curr. Opin. Microbiol. 5: 179–186. Mid1p in determining the site of cell division in fission yeast. Celton-Morizur, S., Racine, V., Sibarita, J.B., and Paoletti, A. J. Cell Biol. 143: 1603–1616. 2006. Pom1 kinase links division plane position to cell Balasubramanian, M.K., Helfman, D.M., and Hemmingsen, S.M. polarity by regulating Mid1p cortical distribution. J. Cell 1992. A new essential for cytokinesis in the Sci. 119: 4710–4718. fission yeast S. pombe. Nature 360: 84–87. Chant, J. 1999. Cell polarity in yeast. Annu. Rev. Cell Dev. Biol. Bement, W.M., Benink, H.A., and von Dassow, G. 2005. A 15: 365–391. microtubule-dependent zone of active RhoA during cleavage Chant, J. and Herskowitz, I. 1991. Genetic control of bud site plane specification. J. Cell Biol. 170: 91–101. selection in yeast by a set of gene products that constitute Bender, A. and Pringle, J.R. 1989. Multicopy suppression of the a morphogenetic pathway. Cell 65: 1203–1212. cdc24 budding defect in yeast by CDC42 and three newly Chen, W., Foss, M., Tseng, K.F., and Zhang, D. 2008. Redundant identified genes including the ras-related gene RSR1. Proc. mechanisms recruit actin into the contractile ring in silk- Natl. Acad. Sci. 86: 9976–9980. worm spermatocytes. PLoS Biol. 6: e209. doi: 10.1371/journal. Ben-Yehuda, S. and Losick, R. 2002. Asymmetric cell division in pbio.0060209. B. subtilis involves a spiral-like intermediate of the cytoki- Cleary, A. 1992. Microtubule and F-actin dynamics at the netic protein FtsZ. Cell 109: 257–266. division site in living Tradescantia stamen hair cells. J. Cell Ben-Yehuda,S., Rudner, D.Z.,and Losick, R. 2003. RacA, a bacterial Sci. 103: 977–988. protein that anchors chromosomes to the cell poles. Science Cleary, A. 1995. F-actin redistributions at the division site in 299: 532–536. living Tradescantia stomatal complexes as revealed by Ben-Yehuda, S., Fujita, M., Liu, X.S., Gorbatyuk, B., Skoko, D., microinjection of rhodamine-phalloidin. Protoplasma 185: Yan, J., Marko, J.F., Liu, J.S., Eichenberger, P., Rudner, D.Z., 152–165. et al. 2005. Defining a centromere-like element in Bacillus Cleary, A.L. and Smith, L.G. 1998. The Tangled1 gene is subtilis by Identifying the binding sites for the chromosome- required for spatial control of cytoskeletal arrays associated anchoring protein RacA. Mol. Cell 17: 773–782. with cell division during maize leaf development. Plant Cell Bernhardt, T.G. and de Boer, P.A. 2005. SlmA, a nucleoid- 10: 1875–1888. associated, FtsZ binding protein required for blocking septal Corbin, B.D., Yu, X.C., and Margolin, W. 2002. Exploring in- ring assembly over chromosomes in E. coli. Mol. Cell 18: tracellular space: Function of the Min system in round- 555–564. shaped Escherichia coli. EMBO J. 21: 1998–2008.

670 GENES & DEVELOPMENT Downloaded from genesdev.cshlp.org on September 26, 2021 - Published by Cold Spring Harbor Laboratory Press

Positioning cytokinesis

Daga, R.R. and Chang, F. 2005. Dynamic positioning of the Ge, W., Chew, T.G., Wachtler, V., Naqvi, S.N., and Balasubra- fission yeast cell division plane. Proc. Natl. Acad. Sci. 102: manian, M.K. 2005. The novel fission yeast protein Pal1p 8228–8232. interacts with Hip1-related Sla2p/End4p and is involved in Daga, R.R., Lee, K.G., Bratman, S., Salas-Pino, S., and Chang, F. cellular morphogenesis. Mol. Biol. Cell 16: 4124–4138. 2006. Self-organization of microtubule bundles in anucleate Gimenez-Abian, M.I., Gimenez-Abian, J.F., Utrilla, L., and De la fission yeast cells. Nat. Cell Biol. 8: 1108–1113. Torre, C. 2004. Nuclear is contingent on the micro- Dajkovic, A., Lan, G., Sun, S.X., Wirtz, D., and Lutkenhaus, J. tubular cycle responsible for plant cytokinesis. Protoplasma 2008. MinC spatially controls bacterial cytokinesis by an- 224: 41–47. tagonizing the scaffolding function of FtsZ. Curr. Biol. 18: Goehring, N.W. and Beckwith, J. 2005. Diverse paths to midcell: 235–244. Assembly of the bacterial cell division machinery. Curr. Biol. Das, T., Payer, B., Cayouette, M., and Harris, W.A. 2003. In vivo 15: R514–R526. doi: 10.1016/j.cub.2005.06.038. time-lapse imaging of cell divisions during neurogenesis in Gong, Y., Mo, C., and Fraser, S.E. 2004. Planar cell polarity the developing zebrafish retina. Neuron 37: 597–609. signalling controls cell division orientation during zebrafish de Boer, P.A., Crossley, R.E., and Rothfield, L.I. 1989. A division gastrulation. Nature 430: 689–693. inhibitor and a topological specificity factor coded for by the Gonzalez, C. 2007. Spindle orientation, asymmetric division and minicell locus determine proper placement of the division tumour suppression in Drosophila stem cells. Nat. Rev. septum in E. coli. Cell 56: 641–649. Genet. 8: 462–472. Dechant, R. and Glotzer, M. 2003. separation and Gregory, J.A., Becker, E.C., and Pogliano, K. 2008. Bacillus subtilis central spindle assembly act in redundant pathways that MinC destabilizes FtsZ-rings at new cell poles and contributes regulate microtubule density and trigger cleavage furrow tothetimingofcelldivision.Genes & Dev. 22: 3475–3488. formation. Dev. Cell 4: 333–344. Guertin, D.A., Trautmann, S., and McCollum, D. 2002. Cytoki- Devore, J.J., Conrad, G.W., and Rappaport, R. 1989. A model for nesis in eukaryotes. Microbiol. Mol. Biol. Rev. 66: 155–178. astral stimulation of cytokinesis in animal cells. J. Cell Biol. Gunning, B.E. and Wick, S.M. 1985. Preprophase bands, phrag- 109: 2225–2232. moplasts, and spatial control of cytokinesis. J. Cell Sci. Diaz, M., Sanchez, Y., Bennett, T., Sun, C.R., Godoy, C., Tamanoi, Suppl. 2: 157–179. F., Duran, A., and Perez, P. 1993. The Schizosaccharomyces Hale, C.A. and de Boer, P.A. 1997. Direct binding of FtsZ to pombe cwg2+ gene codes for the b subunit of a geranylger- ZipA, an essential component of the septal ring structure anyltransferase type I required for b-glucan synthesis. EMBO that mediates cell division in E. coli. Cell 88: 175–185. J. 12: 5245–5254. Hale, C.A., Meinhardt, H., and de Boer, P.A. 2001. Dynamic Drechsel, D.N., Hyman, A.A., Hall, A., and Glotzer, M. 1997. A localization cycle of the cell division regulator MinE in requirement for Rho and Cdc42 during cytokinesis in Xen- Escherichia coli. EMBO J. 20: 1563–1572. opus embryos. Curr. Biol. 7: 12–23. Hardham, A.R. and Gunning, B.E. 1978. Structure of cortical Ebersbach, G., Briegel, A., Jensen, G.J., and Jacobs-Wagner, C. microtubule arrays in plant cells. J. Cell Biol. 77: 14–34. 2008. A self-associating protein critical for chromosome Harkins, H.A., Page, N., Schenkman, L.R., De Virgilio, C., Shaw, attachment, division, and polar organization in Caulobacter. S., Bussey, H., and Pringle, J.R. 2001. Bud8p and Bud9p, Cell 134: 956–968. proteins that may mark the sites for bipolar budding in yeast. Edwards, D.H. and Errington, J. 1997. The Bacillus subtilis Mol. Biol. Cell 12: 2497–2518. DivIVA protein targets to the division septum and controls Hu, Z. and Lutkenhaus, J. 1999. Topological regulation of cell the site specificity of cell division. Mol. Microbiol. 24: 905– division in Escherichia coli involves rapid pole to pole 915. oscillation of the division inhibitor MinC under the control Edwards, D.H., Thomaides, H.B., and Errington, J. 2000. Pro- of MinD and MinE. Mol. Microbiol. 34: 82–90. miscuous targeting of Bacillus subtilis cell division protein Hu, Z. and Lutkenhaus, J. 2001. Topological regulation of cell DivIVA to division sites in Escherichia coli and fission yeast. division in E. coli spatiotemporal oscillation of MinD EMBO J. 19: 2719–2727. requires stimulation of its ATPase by MinE and phospho- Fleming, E.S., Zajac, M., Moschenross, D.M., Montrose, D.C., lipid. Mol. Cell 7: 1337–1343. Rosenberg, D.W., Cowan, A.E., and Tirnauer, J.S. 2007. Hu, Z., Mukherjee, A., Pichoff, S., and Lutkenhaus, J. 1999. The Planar spindle orientation and asymmetric cytokinesis in MinC component of the division site selection system in the mouse small intestine. J. Histochem. Cytochem. 55: Escherichia coli interacts with FtsZ to prevent polymeriza- 1173–1180. tion. Proc. Natl. Acad. Sci. 96: 14819–14824. Foe, V.E. and von Dassow, G. 2008. Stable and dynamic micro- Hu, Z., Saez, C., and Lutkenhaus, J. 2003. Recruitment of MinC, tubules coordinately shape the myosin activation zone an inhibitor of Z-ring formation, to the membrane in during cytokinetic furrow formation. J. Cell Biol. 183: 457– Escherichia coli: Role of MinD and MinE. J. Bacteriol. 185: 470. 196–203. Fu, X., Shih, Y.L., Zhang, Y., and Rothfield, L.I. 2001. The MinE Huang, K.C. and Wingreen, N.S. 2004. Min-protein oscillations ring required for proper placement of the division site is in round bacteria. Phys. Biol. 1: 229–235. a mobile structure that changes its cellular location during Huang, Y., Chew, T.G., Ge, W., and Balasubramanian, M.K. the Escherichia coli division cycle. Proc. Natl. Acad. Sci. 98: 2007. Polarity determinants Tea1p, Tea4p, and Pom1p in- 980–985. hibit division-septum assembly at cell ends in fission yeast. Fujiwara, K. and Pollard, T.D. 1976. Fluorescent antibody local- Dev. Cell 12: 987–996. ization of myosin in the , cleavage furrow, and Iwase, M., Luo, J., Nagaraj, S., Longtine, M., Kim, H.B., Haarer, mitotic spindle of human cells. J. Cell Biol. 71: 848–875. B.K., Caruso, C., Tong, Z., Pringle, J.R., and Bi, E. 2006. Role Fuller, B.G., Lampson, M.A., Foley, E.A., Rosasco-Nitcher, S., Le, of a Cdc42p effector pathway in recruitment of the yeast K.V., Tobelmann, P., Brautigan, D.L., Stukenberg, P.T., and septins to the presumptive bud site. Mol. Biol. Cell 17: 1110– Kapoor, T.M. 2008. Midzone activation of aurora B in 1125. anaphase produces an intracellular phosphorylation gradient. Jiang, W., Jimenez, G., Wells, N.J., Hope, T.J., Wahl, G.M., Nature 453: 1132–1136. Hunter, T., and Fukunaga, R. 1998. PRC1: A human mitotic

GENES & DEVELOPMENT 671 Downloaded from genesdev.cshlp.org on September 26, 2021 - Published by Cold Spring Harbor Laboratory Press

Oliferenko et al.

spindle-associated CDK substrate protein required for cyto- Marks, J., Hagan, I.M., and Hyams, J.S. 1986. Growth polarity kinesis. Mol. Cell 2: 877–885. and cytokinesis in fission yeast: The role of the cytoskeleton. Kawamura, K. 1977. Microdissection studies on the dividing J. Cell Sci. Suppl. 5: 229–241. neuroblast of the grasshopper, with special reference to the Marston, A.L. and Errington, J. 1999. Selection of the midcell mechanism of unequal cytokinesis. Exp. Cell Res. 106: 127– division site in Bacillus subtilis through MinD-dependent 137. polar localization and activation of MinC. Mol. Microbiol. Kimura, K., Ito, M., Amano, M., Chihara, K., Fukata, Y., 33: 84–96. Nakafuku, M., Yamamori, B., Feng, J., Nakano, T., Okawa, Marston, A.L., Thomaides, H.B., Edwards, D.H., Sharpe, M.E., K., et al. 1996. Regulation of myosin phosphatase by Rho and and Errington, J. 1998. Polar localization of the MinD protein Rho-associated kinase (Rho-kinase). Science 273: 245–248. of Bacillus subtilis and its role in selection of the mid-cell Kishi, K., Sasaki, T., Kuroda, S., Itoh, T., and Takai, Y. 1993. division site. Genes & Dev. 12: 3419–3430. Regulation of cytoplasmic division of Xenopus embryo by McCollum, D. and Gould, K.L. 2001. Timing is everything: rho p21 and its inhibitory GDP/GTP exchange protein (rho Regulation of mitotic exit and cytokinesis by the MEN and GDI). J. Cell Biol. 120: 1187–1195. SIN. Trends Cell Biol. 11: 89–95. Kohl, L., Sherwin, T., and Gull, K. 1999. Assembly of the Miller, A.L. and Bement, W.M. 2009. Regulation of cytokinesis paraflagellar rod and the flagellum attachment zone complex by Rho GTPase flux. Nat. Cell Biol. 11: 71–77. during the Trypanosoma brucei cell cycle. J. Eukaryot. Miller, P.J. and Johnson, D.I. 1994. Cdc42p GTPase is involved in Microbiol. 46: 105–109. controlling polarized cell growth in Schizosaccharomyces Kohl, L., Robinson, D., and Bastin, P. 2003. Novel roles for the pombe. Mol. Cell. Biol. 14: 1075–1083. flagellum in cell morphogenesis and cytokinesis of trypano- Mineyuki, Y. 1999. The preprophase band of microtubules: Its somes. EMBO J. 22: 5336–5346. function as a cytokinetic apparatus in higher plants. Int. Rev. Kurasawa, Y., Earnshaw, W.C., Mochizuki, Y., Dohmae, N., and Cytol. 187: 1–49. Todokoro, K. 2004. Essential roles of KIF4 and its binding Minoshima, Y., Kawashima, T., Hirose, K., Tonozuka, Y., partner PRC1 in organized central spindle midzone forma- Kawajiri, A., Bao, Y.C., Deng, X., Tatsuka, M., Narumiya, tion. EMBO J. 23: 3237–3248. S., May Jr., W.S., et al. 2003. Phosphorylation by aurora B La Carbona, S. and Le Goff, X. 2006. Spatial regulation of converts MgcRacGAP to a RhoGAP during cytokinesis. Dev. cytokinesis by the Kin1 and Pom1 kinases in fission yeast. Cell 4: 549–560. Curr. Genet. 50: 377–391. Mishima, M., Kaitna, S., and Glotzer, M. 2002. Central spindle Lackner, L.L., Raskin, D.M., and de Boer, P.A. 2003. ATP- assembly and cytokinesis require a kinesin-like protein/ dependent interactions between Escherichia coli Min pro- RhoGAP complex with microtubule bundling activity. Dev. teins and the phospholipid membrane in vitro. J. Bacteriol. Cell 2: 41–54. 185: 735–749. Mishima, M., Pavicic, V., Gruneberg, U., Nigg, E.A., and Glotzer, Lechler, T. and Fuchs, E. 2005. Asymmetric cell divisions M. 2004. Cell cycle regulation of central spindle assembly. promote stratification and differentiation of mammalian Nature 430: 908–913. skin. Nature 437: 275–280. Moreira-Leite, F.F., Sherwin, T., Kohl, L., and Gull, K. 2001. A Lee, K.S., Yuan, Y.L., Kuriyama, R., and Erikson, R.L. 1995. Plk1 trypanosome structure involved in transmitting cytoplasmic is an M-phase-specific protein kinase and interacts with information during cell division. Science 294: 610–612. a kinesin-like protein, CHO1/MKLP-1. Mol. Cell. Biol. 15: Motegi, F., Mishra, M., Balasubramanian, M.K., and Mabuchi, I. 7143–7151. 2004. Myosin-II reorganization during mitosis is controlled Liakopoulos, D., Kusch, J., Grava, S., Vogel, J., and Barral, Y. temporally by its dephosphorylation and spatially by Mid1 in 2003. Asymmetric loading of Kar9 onto spindle poles and fission yeast. J. Cell Biol. 165: 685–695. microtubules ensures proper spindle alignment. Cell 112: Mukhina, S., Wang, Y.L., and Murata-Hori, M. 2007. a-Actinin is 561–574. required for tightly regulated remodeling of the actin cortical Liu, B. and Palevitz, B. 1992. Organization of cortical microfila- network during cytokinesis. Dev. Cell 13: 554–565. ments in dividing root cells. Cell Motil. Cytoskeleton 23: Murata, T. and Wada, M. 1991. Effects of centrifugation on 252–264. preprophase-band formation in Adiantum protonemata. Liu, X., Zhou, T., Kuriyama, R., and Erikson, R.L. 2004. Planta 183: 391–398. Molecular interactions of Polo-like-kinase 1 with the mitotic Murthy, K. and Wadsworth, P. 2008. Dual role for microtubules kinesin-like protein CHO1/MKLP-1. J. Cell Sci. 117: 3233– in regulating cortical contractility during cytokinesis. J. Cell 3246. Sci. 121: 2350–2359. Loose, M., Fischer-Friedrich, E., Ries, J., Kruse, K., and Schwille, Neef, R., Gruneberg, U., Kopajtich, R., Li, X., Nigg, E.A., Sillje, P. 2008. Spatial regulators for bacterial cell division self- H., and Barr, F.A. 2007. Choice of Plk1 docking partners organize into surface waves in vitro. Science 320: 789–792. during mitosis and cytokinesis is controlled by the activation Lu, B., Roegiers, F., Jan, L.Y., and Jan, Y.N. 2001. Adherens state of Cdk1. Nat. Cell Biol. 9: 436–444. junctions inhibit asymmetric division in the Drosophila O’Connell, C.B. and Wang, Y.L. 2000. Mammalian spindle epithelium. Nature 409: 522–525. orientation and position respond to changes in cell shape in Lutkenhaus, J. 2007. Assembly dynamics of the bacterial Min- a dynein-dependent fashion. Mol. Biol. Cell 11: 1765–1774. CDE system and spatial regulation of the Z ring. Annu. Rev. Odell, G.M. and Foe, V.E. 2008. An agent-based model contrasts Biochem. 76: 539–562. opposite effects of dynamic and stable microtubules on Mabuchi, I. and Okuno, M. 1977. The effect of myosin antibody cleavage furrow positioning. J. Cell Biol. 183: 471–483. on the division of starfish blastomeres. J. Cell Biol. 74: 251– Padte, N.N., Martin, S.G., Howard, M., and Chang, F. 2006. The 263. cell-end factor pom1p inhibits mid1p in specification of the Mabuchi, I., Hamaguchi, Y., Fujimoto, H., Morii, N., Mishima, cell division plane in fission yeast. Curr. Biol. 16: 2480–2487. M., and Narumiya, S. 1993. A rho-like protein is involved in Paluch, E., Piel, M., Prost, J., Bornens, M., and Sykes, C. 2005. the organisation of the contractile ring in dividing sand dollar Cortical actomyosin breakage triggers shape oscillations in eggs. Zygote 1: 325–331. cells and cell fragments. Biophys. J. 89: 724–733.

672 GENES & DEVELOPMENT Downloaded from genesdev.cshlp.org on September 26, 2021 - Published by Cold Spring Harbor Laboratory Press

Positioning cytokinesis

Paoletti, A. and Chang, F. 2000. Analysis of mid1p, a protein Schroeder, T.E. 1968. Cytokinesis: Filaments in the cleavage required for placement of the cell division site, reveals a link furrow. Exp. Cell Res. 53: 272–276. between the nucleus and the cell surface in fission yeast. Schroeder, T.E. 1973. Actin in dividing cells: Contractile ring Mol. Biol. Cell 11: 2757–2773. filaments bind heavy meromyosin. Proc. Natl. Acad. Sci. 70: Park, H.O., Bi, E., Pringle, J.R., and Herskowitz, I. 1997. Two 1688–1692. active states of the Ras-related Bud1/Rsr1 protein bind to Schuyler, S.C. and Pellman, D. 2001. Search, capture and signal: different effectors to determine yeast cell polarity. Proc. Natl. Games microtubules and play. J. Cell Sci. 114: Acad. Sci. 94: 4463–4468. 247–255. Patrick, J.E. and Kearns, D.B. 2008. MinJ (YvjD) is a topological Severson, A.F., Hamill, D.R., Carter, J.C., Schumacher, J., and determinant of cell division in Bacillus subtilis. Mol. Micro- Bowerman, B. 2000. The aurora-related kinase AIR-2 recruits biol. 70: 1166–1179. ZEN-4/CeMKLP1 to the mitotic spindle at metaphase and is Perry, S.E. and Edwards, D.H. 2004. Identification of a polar required for cytokinesis. Curr. Biol. 10: 1162–1171. targeting determinant for Bacillus subtilis DivIVA. Mol. Sharma, R., Peacock, L., Gluenz, E., Gull, K., Gibson, W., and Microbiol. 54: 1237–1249. Carrington, M. 2008. Asymmetric cell division as a route to Petronczki, M. and Knoblich, J.A. 2001. DmPAR-6 directs reduction in cell length and change in cell morphology in epithelial polarity and asymmetric cell division of neuro- trypanosomes. Protist 159: 137–151. blasts in Drosophila. Nat. Cell Biol. 3: 43–49. Sheeman, B., Carvalho, P., Sagot, I., Geiser, J., Kho, D., Hoyt, Petronczki, M., Glotzer, M., Kraut, N., and Peters, J.M. 2007. M.A., and Pellman, D. 2003. Determinants of S. cerevisiae Polo-like kinase 1 triggers the initiation of cytokinesis in dynein localization and activation: Implications for the human cells by promoting recruitment of the RhoGEF Ect2 mechanism of spindle positioning. Curr. Biol. 13: 364–372. to the central spindle. Dev. Cell 12: 713–725. Shih, Y.L., Le, T., and Rothfield, L. 2003. Division site selection Pichoff, S. and Lutkenhaus, J. 2001. Escherichia coli division in Escherichia coli involves dynamic redistribution of Min inhibitor MinCD blocks septation by preventing Z-ring proteins within coiled structures that extend between the formation. J. Bacteriol. 183: 6630–6635. two cell poles. Proc. Natl. Acad. Sci. 100: 7865–7870. Pichoff, S. and Lutkenhaus, J. 2005. Tethering the Z ring to the Shiomi, D. and Margolin, W. 2007. The C-terminal domain of membrane through a conserved membrane targeting se- MinC inhibits assembly of the Z ring in Escherichia coli. J. quence in FtsA. Mol. Microbiol. 55: 1722–1734. Bacteriol. 189: 236–243. Piekny, A., Werner, M., and Glotzer, M. 2005. Cytokinesis: Sipiczki, M., Yamaguchi, M., Grallert, A., Takeo, K., Zilahi, E., Welcome to the Rho zone. Trends Cell Biol. 15: 651–658. Bozsik, A., and Miklos, I. 2000. Role of cell shape in de- Ramirez-Arcos, S., Szeto, J., Beveridge, T., Victor, C., Francis, F., termination of the division plane in Schizosaccharomyces and Dillon, J. 2001. Deletion of the cell-division inhibitor pombe: Random orientation of septa in spherical cells. J. MinC results in lysis of Neisseria gonorrhoeae. Microbiology Bacteriol. 182: 1693–1701. 147: 225–237. Smith, L.G., Hake, S., and Sylvester, A.W. 1996. The tangled-1 Rappaport, R. 1961. Experiments concerning the cleavage stim- mutation alters cell division orientations throughout maize ulus in sand dollar eggs. J. Exp. Zool. 148: 81–89. leaf development without altering leaf shape. Development Rappaport, R. 1985. Repeated furrow formation from a single 122: 481–489. mitotic apparatus in cylindrical sand dollar eggs. J. Exp. Zool. Sohrmann, M., Fankhauser, C., Brodbeck, C., and Simanis, V. 234: 167–171. 1996. The dmf1/mid1 gene is essential for correct positioning Rappaport, R. 1986. Establishment of the mechanism of cytoki- of the division septum in fission yeast. Genes & Dev. 10: nesis in animal cells. Int. Rev. Cytol. 105: 245–281. 2707–2719. Rappaport, R. and Ebstein, R.P. 1965. Duration of stimulus and Suefuji, K., Valluzzi, R., and RayChaudhuri, D. 2002. Dynamic latent periods preceding furrow formation in sand dollar eggs. assembly of MinD into filament bundles modulated by ATP, J. Exp. Zool. 158: 373–382. phospholipids, and MinE. Proc. Natl. Acad. Sci. 99: 16776– Rappaport, R. and Rappaport, B.N. 1993. Duration of division-related 16781. events in cleaving sand dollar eggs. Dev. Biol. 158: 265–273. Sun, Q. and Margolin, W. 2004. Effects of perturbing nucleoid Raskin, D.M. and de Boer, P.A. 1997. The MinE ring: An FtsZ- structure on nucleoid occlusion-mediated toporegulation of independent cell structure required for selection of the FtsZ ring assembly. J. Bacteriol. 186: 3951–3959. correct division site in E. coli. Cell 91: 685–694. Szollosi, D., Calarco, P., and Donahue, R.P. 1972. Absence of Raskin, D.M. and de Boer, P.A. 1999. MinDE-dependent pole-to- in the first and second meiotic spindles of mouse pole oscillation of division inhibitor MinC in Escherichia oocytes. J. Cell Sci. 11: 521–541. coli. J. Bacteriol. 181: 6419–6424. Terenna, C.R., Makushok, T., Velve-Casquillas, G., Baigl, D., Reinsch, S. and Karsenti, E. 1994. Orientation of spindle axis and Chen, Y., Bornens, M., Paoletti, A., Piel, M., and Tran, P.T. distribution of plasma membrane proteins during cell division 2008. Physical mechanisms redirecting cell polarity and cell in polarized MDCKII cells. J. Cell Biol. 126: 1509–1526. shape in fission yeast. Curr. Biol. 18: 1748–1753. Royou, A., Field, C., Sisson, J.C., Sullivan, W., and Karess, R. Thanbichler, M. and Shapiro, L. 2006. MipZ, a spatial regulator 2004. Reassessing the role and dynamics of nonmuscle coordinating chromosome segregation with cell division in myosin II during furrow formation in early Drosophila Caulobacter. Cell 126: 147–162. embryos. Mol. Biol. Cell 15: 838–850. Thery, M., Racine, V., Pepin, A., Piel, M., Chen, Y., Sibarita, J.B., Schlesinger, A., Shelton, C.A., Maloof, J.N., Meneghini, M., and and Bornens, M. 2005. The extracellular matrix guides the Bowerman, B. 1999. Wnt pathway components orient a mi- orientation of the cell division axis. Nat. Cell Biol. 7: 947– totic spindle in the early Caenorhabditis elegans embryo 953. without requiring gene in the responding cell. Thery, M., Jimenez-Dalmaroni, A., Racine, V., Bornens, M., and Genes & Dev. 13: 2028–2038. Julicher, F. 2007. Experimental and theoretical study of Schober, M., Schaefer, M., and Knoblich, J.A. 1999. Bazooka mitotic spindle orientation. Nature 447: 493–496. recruits Inscuteable to orient asymmetric cell divisions in Thomaides, H.B., Freeman, M., El Karoui, M., and Errington, J. Drosophila neuroblasts. Nature 402: 548–551. 2001. Division site selection protein DivIVA of Bacillus

GENES & DEVELOPMENT 673 Downloaded from genesdev.cshlp.org on September 26, 2021 - Published by Cold Spring Harbor Laboratory Press

Oliferenko et al.

subtilis has a second distinct function in chromosome Yeh, E., Yang, C., Chin, E., Maddox, P., Salmon, E.D., Lew, D.J., segregation during sporulation. Genes & Dev. 15: 1662–1673. and Bloom, K. 2000. Dynamic positioning of mitotic spindles Tolic-Nørrelykke, I.M., Sacconi, L., Stringari, C., Raabe, I., and in yeast: Role of microtubule motors and cortical determi- Pavone, F.S. 2005. Nuclear and division-plane positioning nants. Mol. Biol. Cell 11: 3949–3961. revealed by optical micromanipulation. Curr. Biol. 15: 1212– Yu, X.C. and Margolin, W. 1999. FtsZ ring clusters in min and 1216. partition mutants: Role of both the Min system and the Tong, Z., Gao, X.D., Howell, A.S., Bose, I., Lew, D.J., and Bi, E. nucleoid in regulating FtsZ ring localization. Mol. Microbiol. 2007. Adjacent positioning of cellular structures enabled by 32: 315–326. a Cdc42 GTPase-activating protein-mediated zone of inhibi- tion. J. Cell Biol. 179: 1375–1384. Tran, P.T., Marsh, L., Doye, V., Inoue, S., and Chang, F. 2001. A mechanism for nuclear positioning in fission yeast based on microtubule pushing. J. Cell Biol. 153: 397–411. Vaughan, S. and Gull, K. 2003. The trypanosome flagellum. J. Cell Sci. 116: 757–759. Verde, F., Wiley, D.J., and Nurse, P. 1998. Fission yeast orb6, a ser/thr protein kinase related to mammalian rho kinase and myotonic dystrophy kinase, is required for maintenance of cell polarity and coordinates cell morphogenesis with the cell cycle. Proc. Natl. Acad. Sci. 95: 7526–7531. Verni, F., Somma, M.P., Gunsalus, K.C., Bonaccorsi, S., Belloni, G., Goldberg, M.L., and Gatti, M. 2004. Feo, the Drosophila homolog of PRC1, is required for central-spindle formation and cytokinesis. Curr. Biol. 14: 1569–1575. Walker, K.L., Muller, S., Moss, D., Ehrhardt, D.W., and Smith, L.G. 2007. Arabidopsis TANGLED identifies the division plane throughout mitosis and cytokinesis. Curr. Biol. 17: 1827–1836. Wang, Y.L. 2005. The mechanism of cortical ingression during early cytokinesis: Thinking beyond the contractile ring hypothesis. Trends Cell Biol. 15: 581–588. Watanabe, N., Madaule, P., Reid, T., Ishizaki, T., Watanabe, G., Kakizuka, A., Saito, Y., Nakao, K., Jockusch, B.M., and Narumiya, S. 1997. p140mDia, a mammalian homolog of Drosophila diaphanous, is a target protein for Rho small GTPase and is a ligand for . EMBO J. 16: 3044–3056. White, J.G. and Borisy, G.G. 1983. On the mechanisms of cytokinesis in animal cells. J. Theor. Biol. 101: 289–316. White, O., Eisen, J.A., Heidelberg, J.F., Hickey, E.K., Peterson, J.D., Dodson, R.J., Haft, D.H., Gwinn, M.L., Nelson, W.C., Richardson, D.L., et al. 1999. Genome sequence of the radioresistant bacterium Deinococcus radiodurans R1. Sci- ence 286: 1571–1577. Woldringh, C.L., Mulder, E., Huls, P.G., and Vischer, N. 1991. Toporegulation of bacterial division according to the nucle- oid occlusion model. Res. Microbiol. 142: 309–320. Wolpert, L. 1960. The mechanics and mechanism of cleavage. Int. Rev. Cytol. 10: 163–216. Wu, L.J. and Errington, J. 2003. RacA and the Soj–Spo0J system combine to effect polar chromosome segregation in sporu- lating Bacillus subtilis. Mol. Microbiol. 49: 1463–1475. Wu, L.J. and Errington, J. 2004. Coordination of cell division and chromosome segregation by a nucleoid occlusion protein in Bacillus subtilis. Cell 117: 915–925. Yamashita, Y.M. and Fuller, M.T. 2005. Asymmetric stem cell division and function of the niche in the Drosophila male germ line. Int. J. Hematol. 82: 377–380. Yamashita, Y.M. and Fuller, M.T. 2008. Asymmetric centrosome behavior and the mechanisms of stem cell division. J. Cell Biol. 180: 261–266. Yamashita, Y.M., Jones, D.L., and Fuller, M.T. 2003. Orientation of asymmetric stem cell division by the APC tumor suppres- sor and centrosome. Science 301: 1547–1550. Yamashita, Y.M., Mahowald, A.P., Perlin, J.R., and Fuller, M.T. 2007. Asymmetric inheritance of mother versus daughter centrosome in stem cell division. Science 315: 518–521.

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Positioning cytokinesis

Snezhana Oliferenko, Ting Gang Chew and Mohan K. Balasubramanian

Genes Dev. 2009, 23: Access the most recent version at doi:10.1101/gad.1772009

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