Downloaded from genesdev.cshlp.org on September 26, 2021 - Published by Cold Spring Harbor Laboratory Press REVIEW Positioning cytokinesis 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 cell 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 chromosomes 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 cell division 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 bacteria, the tubulin-like protein FtsZ assem- model organisms and model cell types. bles into a ring structure that is perpendicular to the axis of chromosome 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 proteins (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 microtubule-based motors, such as kinesins and dyneins, 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 cell wall) 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, microtubules 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-actin 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 cytoskeleton 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 myosin, and several other proteins assemble into In many cell types, prokaryotes and eukaryotes 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 Bacillus subtilis 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 660 GENES & DEVELOPMENT 23:660–674 Ó 2009 by Cold Spring Harbor Laboratory Press ISSN 0890-9369/09; www.genesdev.org Downloaded from genesdev.cshlp.org on September 26, 2021 - Published by Cold Spring Harbor Laboratory Press 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 nucleoid occlusion division. prevents Z-ring assembly in the vicinity of the nucleoids (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 gene 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 Kinesin Dynein 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 fission yeast. bFunctions in mitotic spindle positioning and cytokinetic fidelity in budding yeast. GENES & DEVELOPMENT 661 Downloaded from genesdev.cshlp.org on September 26, 2021 - Published by Cold Spring Harbor Laboratory Press Oliferenko et al. 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.