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How dividing cells stay in shape Studies of the mechanism of cytokinesis, the process by which a mother cell undergoes cleavage to form two separated daughter cells, often focus on the action of the contractile actomyosin ring at the cell equator. Ewa Paluch and colleagues instead investigate the mechanics of the actomyosin cortex found at the cell poles during cytokinesis. They find that the presence of a contractile polar cortex makes cytokinesis an inherently unstable process that can result in misalignment of the constriction ring. They propose that the membrane blebs forming at the poles of dividing cells stabilize the position by releasing cortical contractility. These findings reveal an inherent instability in the shape of a dividing cell and demonstrate a novel mechanism that helps to limit shape instability. Cytokinesis, the physical separation of daughter cells at the end of mitosis, requires precise regulation of the mechanical properties of the cell periphery 1 , 2 . Although studies of cytokinetic mechanics mostly focus on the equatorial constriction ring 3 , a contractile actomyosin cortex is also present at the poles of dividing cells 2 , 4 . Whether polar forces influence cytokinetic cell shape and furrow positioning remains an open question. Here we demonstrate that the polar cortex makes cytokinesis inherently unstable. We show that limited asymmetric polar contractions occur during cytokinesis, and that perturbing the polar cortex leads to cell shape oscillations, resulting in furrow displacement and aneuploidy. A theoretical model based on a competition between cortex turnover and contraction dynamics accurately accounts for the oscillations. We further propose that membrane blebs, which commonly form at the poles of dividing cells 5 and whose role in cytokinesis has long been enigmatic, stabilize cell shape by acting as valves releasing cortical contractility. Our findings reveal an inherent instability in the shape of the dividing cell and unveil a novel, spindle-independent mechanism ensuring the stability of cleavage furrow positioning.

Actomyosin contractility generated cooperatively by nonmuscle myosin II and actin filaments plays essential roles in a wide range of biological processes, such as cell motility, cytokinesis, and tissue morphogenesis. However, subcellular dynamics of actomyosin contractility underlying such processes remains elusive. Here, we demonstrate an optogenetic method to induce relaxation of actomyosin contractility at the subcellular level. The system, named OptoMYPT, combines a protein phosphatase 1c (PP1c)-binding domain of MYPT1 with an optogenetic dimerizer, so that it allows light-dependent recruitment of endogenous PP1c to the plasma membrane. Blue-light illumination is sufficient to induce dephosphorylation of myosin regulatory light chains and a decrease in actomyosin contractile force in mammalian cells and Xenopus embryos. The OptoMYPT system is further employed to understand the mechanics of actomyosin-based cortical tension and contractile ring tension during cytokinesis. We find that the relaxation of cortical tension at both poles by OptoMYPT accelerated the furrow ingression rate, revealing that the cortical tension substantially antagonizes constriction of the cleavage furrow. Based on these results, the OptoMYPT system provides opportunities to understand cellular and tissue mechanics. The subcellular dynamics of actomyosin contractility is currently hard to study. Here the authors report OptoMYPT, an optogenetic method to induce relaxation of actomyosin contractility by allowing light-dependent recruitment of endogenous protein phosphatase 1c (PP1c) to the plasma membrane.

CEP55 was initially identified as a pivotal component of abscission, the final stage of cytokinesis, serving to regulate the physical separation of two daughter cells. Over the past 10 years, several studies have illuminated additional roles for CEP55 including regulating the PI3K/AKT pathway and midbody fate. Concurrently, CEP55 has been studied in the context of cancers including those of the breast, lung, colon and liver. CEP55 overexpression has been found to significantly correlate with tumor stage, aggressiveness, metastasis and poor prognosis across multiple tumor types and therefore has been included as part of several prognostic ‘gene signatures’ for cancer. Here by discussing in depth the functions of CEP55 across different effector pathways, and also its roles as a biomarker and driver of tumorigenesis, we assemble an exhaustive review, thus commemorating a decade of research on CEP55.

The PtdIns(4,5)P 2 5-phosphatase OCRL, mutated in Lowe syndrome, is implicated in trafficking and associates with Rab GTPases. OCRL function is now extended to cytokinesis, where it controls abscission of the intercellular bridge downstream of Rab35 through the local reduction of both PtdIns(4,5)P 2 levels and actin accumulation. Abscission is the least understood step of cytokinesis. It consists of the final cut of the intercellular bridge connecting the sister cells at the end of mitosis, and is thought to involve membrane trafficking as well as lipid and cytoskeleton remodelling 1 , 2 , 3 , 4 , 5 , 6 . We previously identified the Rab35 GTPase as a regulator of a fast recycling endocytic pathway that is essential for post-furrowing cytokinesis stages 7 . Here, we report that the phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P 2 ) 5-phosphatase OCRL, which is mutated in Lowe syndrome patients 8 , 9 , is an effector of the Rab35 GTPase in cytokinesis abscission. GTP-bound (active) Rab35 directly interacts with OCRL and controls its localization at the intercellular bridge. Depletion of Rab35 or OCRL inhibits cytokinesis abscission and is associated with local abnormal PtdIns(4,5)P 2 and F-actin accumulation in the intercellular bridge. These division defects are also found in cell lines derived from Lowe patients and can be corrected by the addition of low doses of F-actin depolymerization drugs. Our data demonstrate that PtdIns(4,5)P 2 hydrolysis is important for normal cytokinesis abscission to locally remodel the F-actin cytoskeleton in the intercellular bridge. They also reveal an unexpected role for the phosphatase OCRL in cell division and shed new light on the pleiotropic phenotypes associated with Lowe disease.

Key Points All cells must divide to proliferate, and most bacteria divide by splitting themselves into two during cytokinesis. Many bacteria divide by splitting into approximately equal halves in a process called binary fission. Cytokinesis in bacteria is achieved by the divisome, a dedicated protein machine that is located at the site of cell division. Recent advances in ultrastructural imaging, biochemistry and genetics of Escherichia coli and other model bacterial species have helped to refine models of divisome function and regulation. FtsZ, the bacterial homologue of tubulin, is the principal driver of bacterial cytokinesis. In vitro , FtsZ assembles into single protofilaments in the presence of GTP. In vivo , these protofilaments loosely assemble to encircle the cell at the site of division — called the Z ring — and are positioned there by species-specific spatial positioning proteins. As FtsZ is a soluble protein, FtsZ protofilaments must be tethered to the inner surface of the cytoplasmic membrane by additional proteins, including FtsA and ZipA in E. coli . This complex of FtsZ and membrane tethers is called the proto-ring and has highly dynamic behaviour. Although they do not form microtubules, FtsZ protofilaments self-associate to form bundles, either through interactions with other FtsZ subunits or with several FtsZ-binding proteins that enhance bundling, including ZipA and Zap proteins. These lateral interactions between FtsZ protofilaments may be important for the ability of FtsZ to divide a cell. FtsA, a bacterial homologue of actin, is a key connector between the Z ring and other proteins of the divisome, all of which span the membrane and some of which bind to the peptidoglycan layer. Once the divisome is completely assembled, it coordinates the inward constriction of the Z ring and cytoplasmic membrane with the synthesis of the cell division septum, which is composed of peptidoglycan. FtsA is a key player in this coordination, which probably involves feedback signalling between the peptidoglycan-binding divisome proteins and the Z ring. Biochemical characterization of FtsA remains a major challenge. In addition to signalling in the divisome during the process of cytokinesis, the divisome is regulated by mechanical, metabolic and stress inputs. FtsZ is a major target for these regulators, but other divisome proteins are also targets. Understanding how divisome proteins are inhibited or stimulated will be valuable in the future design of divisome-specific antimicrobial compounds. Bacterial cell division occurs under tight temporal and spatial regulation by the divisome. In this Review, Haeusser and Margolin review the structure and function of the divisome, highlighting insights into the assembly of this multicomponent machinery that were provided by recent technical advances. Bacteria must divide to increase in number and colonize their niche. Binary fission is the most widespread means of bacterial cell division, but even this relatively simple mechanism has many variations on a theme. In most bacteria, the tubulin homologue FtsZ assembles into a ring structure, termed the Z ring, at the site of cytokinesis and recruits additional proteins to form a large protein machine — the divisome — that spans the membrane. In this Review, we discuss current insights into the regulation of the assembly of the Z ring and how the divisome drives membrane invagination and septal cell wall growth while flexibly responding to various cellular inputs.

Chromosome folding is modulated as cells progress through the cell cycle. During mitosis, condensins fold chromosomes into helical loop arrays. In interphase, the cohesin complex generates loops and topologically associating domains (TADs), while a separate process of compartmentalization drives segregation of active and inactive chromatin. We used synchronized cell cultures to determine how the mitotic chromosome conformation transforms into the interphase state. Using high-throughput chromosome conformation capture (Hi-C) analysis, chromatin binding assays and immunofluorescence, we show that, by telophase, condensin-mediated loops are lost and a transient folding intermediate is formed that is devoid of most loops. By cytokinesis, cohesin-mediated CTCF–CTCF loops and the positions of TADs emerge. Compartment boundaries are also established early, but long-range compartmentalization is a slow process and proceeds for hours after cells enter G1. Our results reveal the kinetics and order of events by which the interphase chromosome state is formed and identify telophase as a critical transition between condensin- and cohesin-driven chromosome folding. Abramo et al. show that during mitosis, condensin-mediated loops are lost by telophase and a transient chromosome folding intermediate is formed that lacks cohesin-generated loops.

During cytokinesis in plants, trans-Golgi network-derived vesicles accumulate at the center of dividing cells and undergo various structural changes to give rise to the planar cell plate. However, how this conversion occurs at the molecular level remains elusive. In this study, we report that SH3 Domain-Containing Protein 2 (SH3P2) in Arabidopsis thaliana plays a crucial role in converting vesicles to the planar cell plate. SH3P2 RNAi plants showed cytokinesis-defective phenotypes and produced aggregations of vesicles at the leading edge of the cell plate. SH3P2 localized to the leading edge of the cell plate, particularly the constricted or curved regions of the cell plate. The BAR domain of SH3P2 induced tubulation of vesicles. SH3P2 formed a complex with dynamin-related protein 1A (DRP1A) and affected DRP1A accumulation to the cell plate. Based on these results, we propose that SH3P2 functions together with DRP1A to convert the fused vesicles to tubular structures during cytokinesis.

New techniques for obtaining electron microscopy data through the cell volume are being increasingly utilized to answer cell biologic questions. Here, we present a three-dimensional atlas of Plasmodium falciparum ultrastructure throughout parasite cell division. Multiple wild type schizonts at different stages of segmentation, or budding, were imaged and rendered, and the 3D structure of their organelles and daughter cells are shown. Our high-resolution volume electron microscopy both confirms previously described features in 3D and adds new layers to our understanding of Plasmodium nuclear division. Interestingly, we demonstrate asynchrony of the final nuclear division, a process that had previously been reported as synchronous. Use of volume electron microscopy techniques for biological imaging is gaining prominence, and there is much we can learn from applying them to answer questions about Plasmodium cell biology. We provide this resource to encourage readers to consider adding these techniques to their cell biology toolbox.

Bacterial cytokinesis is accomplished by the essential ‘divisome’ machinery. The most widely conserved divisome component, FtsZ, is a tubulin homolog that polymerizes into the ‘FtsZ-ring’ (‘Z-ring’). Previous in vitro studies suggest that Z-ring contraction serves as a major constrictive force generator to limit the progression of cytokinesis. Here, we applied quantitative superresolution imaging to examine whether and how Z-ring contraction limits the rate of septum closure during cytokinesis in Escherichia coli cells. Surprisingly, septum closure rate was robust to substantial changes in all Z-ring properties proposed to be coupled to force generation: FtsZ’s GTPase activity, Z-ring density, and the timing of Z-ring assembly and disassembly. Instead, the rate was limited by the activity of an essential cell wall synthesis enzyme and further modulated by a physical divisome–chromosome coupling. These results challenge a Z-ring–centric view of bacterial cytokinesis and identify cell wall synthesis and chromosome segregation as limiting processes of cytokinesis.

Cytokinesis is the process by which mitotic cells physically split in two following chromosome segregation. Dividing animal cells first ingress a cytokinetic furrow and then separate the plasma membrane by abscission. The general cytological events and several conserved molecular factors involved in cytokinesis have been known for many years. However, recent progress in microscopy, chemical genetics, biochemical reconstitution and biophysical methodology has tremendously increased our understanding of the underlying molecular mechanisms. We discuss how recent insights have led to refined models of the distinct steps of animal cell cytokinesis, including anaphase spindle reorganization, division plane specification, actomyosin ring assembly and contraction, and abscission. We highlight how molecular signalling pathways coordinate the individual events to ensure faithful partitioning of the genome to emerging daughter cells.