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Membrane Traffic: a Driving Force in Cytokinesis Review TRENDS in Cell Biology Vol.15 No.2 February 2005 Cytokinesis series Membrane traffic: a driving force in cytokinesis Roger Albertson, Blake Riggs and William Sullivan Department of Molecular, Cellular and Developmental Biology, University of California, Santa Cruz, CA 95064, USA Dividing animal and plant cells maintain a constant cytokinesis is the fact that secretion remains active chromosome content through temporally separated throughout the cell cycle in plants but is dramatically rounds of replication and segregation. Until recently, downregulated during mitosis in animal cells [2,3]. the mechanisms by which animal and plant cells Recent advances in microscopy, a new generation of maintain a constant surface area have been considered fluorescent probes and sophisticated functional to be distinct. The prevailing view was that surface area approaches have begun to highlight the similarities was maintained in dividing animal cells through tem- between plant and animal cytokinesis. Specifically, porally separated rounds of membrane expansion and studies of a variety of animal systems have revealed membrane invagination. The latter event, known as that, like plants, membrane trafficking has an important cytokinesis, produces two physically distinct daughter role during animal cytokinesis (Figures 1,2 and Tables 1,2). cells and has been thought to be primarily driven by These studies demonstrate that targeted membrane actomyosin-based constriction. By contrast, membrane addition during cleavage furrow formation is a funda- addition seems to be the primary mechanism that drives mental and widely conserved mechanism of animal cytokinesis in plants and, thus, the two events are linked cytokinesis. This insight has opened new avenues of mechanistically and temporally. In this article (which is investigation that are now rapidly being addressed: part of the Cytokinesis series), we discuss recent studies what are the sources of membrane; when and where is of a variety of organisms that have made a convincing membrane added and removed during cytokinesis; how do case for membrane trafficking at the cleavage furrow membrane-trafficking pathways regulate membrane being a key component of both animal and plant delivery to and from the cleavage furrow; what role does cytokinesis. the cytoskeleton have in this process; and why are the distinct protein and lipid compositions at the furrow important for cytokinesis? In this article, we highlight Introduction recent progress in these areas (for further reviews about Basic light-microscopic observations highlight the differ- specific aspects of plant and animal cytokinesis, see Refs ences between plant and animal cytokinesis. During plant [3–9]). cell division, a specialized structure known as the phragmoplast forms at the cell center. The phragmoplast Cytokinesis in animal cells often requires on-time consists of membrane, microtubules and microfilaments, delivery of Golgi-derived membrane and promotes the concentration and fusion of secretory The additional membrane required for cytokinesis has vesicles [1]. Thus, plant cytokinesis proceeds from the cell several possible origins such as excess membrane stored center towards the cortex, relying primarily on vesicle within the plasma membrane, and internal membrane fusion. This process involves delivery of cell wall and derived from secretory, endocytic or recycling pathways membrane components, and requires actomyosin for (Figure 2). In amphibian embryos, microvilli observed expansion and fusion of the newly formed membrane during the initiation of cytokinesis might provide the with the plasma membrane. By contrast, cytokinesis in required membrane [10].IncellularizingDrosophila animal cells relies on a pronounced actomyosin contractile embryos, excess membrane stored as microprojections is ring that drives plasma membrane invagination from the a possible source [11]. Studies have also emphasized the cortex. An important feature of this ‘purse-string’ model is role of vesicle-mediated delivery of membrane from that, with the exception of the terminal sealing event, it internal pools during cytokinesis [12–16] (Table 1). does not require cleavage furrow ingression and mem- Perhaps the most striking evidence comes from scanning brane addition to be linked temporally and spatially. electron microscopy (SEM) and live confocal microscopy According to this basic model, additional membrane could studies of Xenopus embryos that demonstrate large be incorporated at any time and anywhere along the clusters of exocytic fusion pores near the base of the plasma membrane before the terminal events of cytokin- invaginating furrow [17] (Figure 3a). These are the sites of esis. Reinforcing the distinction between plant and animal recent exocytic events that required microtubules. Esti- Corresponding author: Sullivan, W. ([email protected]). mates based on fusion pore distribution and density Available online 6 January 2005 suggest that localized exocytosis is sufficient to provide www.sciencedirect.com 0962-8924/$ - see front matter Q 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.tcb.2004.12.008 Review TRENDS in Cell Biology Vol.15 No.2 February 2005 93 furrow regression occurs [20]. Because BFA treatment also results in ectopic furrowing, it is unlikely that defects Plasma t-SNARE during the terminal stages of cytokinesis are due to a membrane Endocytic vesicle v-SNARE general lack of membrane; it is more likely that they are caused by a specific requirement for Golgi-derived vesicles RE at this stage. Whereas Golgi-based vesicle delivery is crucial during the terminal stages of embryonic C. elegans cytokinesis, it is required for the initial stages of furrow progression in Late Drosophila spermatocytes. Mutants for four way stop endosome Early endosme (fws), a Cog5 (conserved oligomeric Golgi) homolog, establish cleavage furrows, although ingression fails in these mutants [21] (Figure 1f). Mammalian Cog5 is a member of an eight-protein Golgi-associated complex believed to have a role in Golgi vesicle targeting [22]. Cog5 is nonessential but increases the efficiency of Golgi- Secretory vesicle based trafficking. Similarly, Fws is not generally required for cytokinesis and cell division throughout Drosophila development, raising the possibility that the large (20 mm) and rapidly cleaving (20 min) spermatocytes place excep- Lysosome Golgi tional demands on Golgi-based vesicle trafficking during cytokinesis. fws mutations also disrupt spermatid elongation – a process that requires extensive membrane addition. Further supporting the role of Golgi-based vesicle trafficking in spermatocyte cytokinesis is the finding that hypomorphic mutations in the Drosophila syntaxin5 homolog, a Golgi-localized soluble N-ethyl- maleimide-sensitive factor attachment protein receptor ER (SNARE) required for ER-to-Golgi traffic, result in male sterility due to failed cytokinesis [23]. In cellularizing Drosophila embryos, there is accumu- lating evidence that indicates that Golgi-mediated mem- brane delivery is required throughout the process of Nucleus furrow invagination. Cellularization is a specialized form of cytokinesis in which furrows that are compositionally TRENDS in Cell Biology and structurally equivalent to cleavage furrows encom- Figure 1. Intracellular membrane-trafficking pathways. Components of secretory, pass the w6000 interphase nuclei aligned on the cortex. endocytic, lysosomal and recycling pathways are shown. Transport steps are Electron microscopy (EM) studies indicate that some of indicated by arrows. Secretion involves vesicle transport from the ER to the Golgi apparatus and then to the plasma membrane. Vesicle fusion involves membrane- the membrane required for cellularization is derived from specific t-SNARE and v-SNARE (blue and red, respectively) protein interactions that extensive microprojections. However, quantifications of are promoted through several adaptor proteins (not shown). Endocytic vesicles cell surface area indicate that excess plasma membrane is budding from the plasma membrane are coated with clathrin (green); clathrin coats include a membrane-specific complex of adaptor proteins (not shown). The GTPase insufficient to complete cell division; thus, it is likely that dynamin assembles into rings (orange) at the neck of clathrin-coated endocytic additional internal stores are also required [11]. Live vesicles; dynamin ring constriction facilitates the ‘pinching off’ of vesicles from the analysis of Golgi movement during cellularization shows plasma membrane. One destination for endocytic vesicles is the early endosome, which directs vesicles back to the plasma membrane (through the RE) or to that Golgi move towards and closely associate with the lysosomes for degradation. advancing furrow, suggesting that they might be a source of membrane [15]. BFA injections severely disrupt most of the new membrane required to complete cyto- cellularization, providing functional support for this kinesis. These and other studies clearly demonstrate that interpretation [15]. Functional studies using antibodies major vesicle addition is associated with cleavage furrow directed against a Drosophila Golgi-associated protein, formation [18]. Lava Lamp, result in severe disruptions of Golgi mor- Golgi-derived vesicles are the primary source of phology and distribution, in addition to failed furrow membrane in plant cytokinesis [5]. Evidence of a similar formation [15]. A separate study using fluorescent surface role in animal cytokinesis came initially
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