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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.

Asymmetric cell division, which includes cell polarization and cytokinesis, is essential for generating cell diversity during development. The budding yeast Saccharomyces cerevisiae reproduces by asymmetric cell division, and has thus served as an attractive model for unraveling the general principles of eukaryotic cell polarization and cytokinesis. Polarity development requires G-protein signaling, cytoskeletal polarization, and exocytosis, whereas cytokinesis requires concerted actions of a contractile actomyosin ring and targeted membrane deposition. In this chapter, we discuss the mechanics and spatial control of polarity development and cytokinesis, emphasizing the key concepts, mechanisms, and emerging questions in the field.

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.

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.

Key Points Live cell imaging studies showed that mitochondria are highly dynamic organelles that frequently fuse and divide. Two evolutionarily conserved large GTPases constitute the core machinery of fusion: mitofusins are found in the outer membrane, and Mgm1 and optic atrophy protein 1 (OPA1) are found in the inner membrane of yeast and mammals, respectively. Mitochondrial fission is mediated by dynamin-related proteins (DRPs) and cofactors that are required for assembly of DRP rings and spirals on the mitochondrial surface. Only little is known about division of the inner membrane. The machineries of mitochondrial fusion and fission are regulated by many cellular pathways, including proteolytic processing, ubiquitylation, sumoylation, phosphorylation and dephosphorylation. Mitochondrial fusion and fission are required for faithful inheritance and proper intracellular distribution of the organelle. Mitochondrial dynamics counteracts cellular ageing by allowing complementation of gene products after fusion of impaired mitochondria, and it constitutes an important part of organellar quality control as it facilitates the elimination of damaged mitochondria by autophagy. Furthermore, mitochondrial division is an important step in apoptosis. Dysfunctions of mitochondrial dynamics contribute to several inherited and age-associated neurodegenerative diseases. The continuous fusion and fission of mitochondria is important for their inheritance and function. The core components of the fusion and fission machineries, and the mechanisms that regulate these processes, have recently been elucidated and found to be integral for the maintenance of cellular quality control. Mitochondria are dynamic organelles that constantly fuse and divide. These processes (collectively termed mitochondrial dynamics) are important for mitochondrial inheritance and for the maintenance of mitochondrial functions. The core components of the evolutionarily conserved fusion and fission machineries have now been identified, and mechanistic studies have revealed the first secrets of the complex processes that govern fusion and fission of a double membrane-bound organelle. Mitochondrial dynamics was recently recognized as an important constituent of cellular quality control. Defects have detrimental consequences on bioenergetic supply and contribute to the pathogenesis of neurodegenerative diseases. These findings open exciting new directions to explore mitochondrial biology.

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.

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.

Key Points The APC/C (anaphase-promoting complex; also known as the cyclosome) is an E3 ubiquitin ligase that mediates the ubiquitylation of key substrates for their degradation by the proteasome at precise times during mitotic progression. Although APC/C activity is most apparent in targeting securin and cyclin B1 to promote anaphase and mitotic exit, the APC/C functions throughout mitosis. Spatiotemporal regulation of APC/C activity promotes substrate degradation at defined times within distinct cellular compartments. The APC/C has several positive and negative regulators, including kinases and protein phosphatases, binding with co-activators CDC20 or CDC20 homologue 1 (CDH1), and with inhibitors such as the mitotic checkpoint complex (MCC). Co-activator proteins recruit substrates to the APC/C and cause conformational changes in the APC/C, fostering increased activity of the E2 ubiquitin-conjugating enzymes that initiate and elongate ubiquitin chains on substrates. The MCC is the effector of the spindle checkpoint signalling pathway. Binding of the MCC to the APC/C inhibits substrate recruitment and ubiquitin chain formation. Dynamic turnover of the MCC, which is partly due to the synthesis and degradation of CDC20, is essential for timely targeting of securin and cyclin B1 after silencing of the spindle checkpoint when chromosomes align at metaphase. The anaphase-promoting complex (also known as the cyclosome) is an E3 ubiquitin ligase that has a crucial function in the regulation of mitosis, particularly during anaphase and mitotic exit. Its activity is tightly controlled by several factors to ensure the timely degradation of key mitotic regulators and thus the proper progression of mitotic events. The appropriate timing of events that lead to chromosome segregation during mitosis and cytokinesis is essential to prevent aneuploidy, and defects in these processes can contribute to tumorigenesis. Key mitotic regulators are controlled through ubiquitylation and proteasome-mediated degradation. The APC/C (anaphase-promoting complex; also known as the cyclosome) is an E3 ubiquitin ligase that has a crucial function in the regulation of the mitotic cell cycle, particularly at the onset of anaphase and during mitotic exit. Co-activator proteins, inhibitor proteins, protein kinases and phosphatases interact with the APC/C to temporally and spatially control its activity and thus ensure accurate timing of mitotic events.

Cell number is a critical factor that determines kernel size in maize (Zea mays). Rapid mitotic divisions in early endosperm development produce most of the cells that make up the starchy endosperm; however, the mechanisms underlying early endosperm development remain largely unknown. We isolated a maize mutant that shows a varied-kernel-size phenotype (vks1). Vks1 encodes ZmKIN11, which belongs to the kinesin-14 subfamily and is predominantly expressed in early endosperm development. VKS1 dynamically localizes to the nucleus and microtubules and plays key roles in the migration of free nuclei in the coenocyte as well as in mitosis and cytokinesis in early mitotic divisions. Absence of VKS1 has relatively minor effects on plants but causes deformities in spindle assembly, sister chromatid separation, and phragmoplast formation in early endosperm development, thereby resulting in reduced cell proliferation. Severities of aberrant mitosis and cytokinesis within individual vks1 endosperms differ, thereby resulting in varied kernel sizes. Our discovery highlights VKS1 as a central regulator of mitosis in early maize endosperm development and provides a potential approach for future yield improvement.

The midbody is an organelle assembled at the intercellular bridge between the two daughter cells at the end of mitosis. It controls the final separation of the daughter cells and has been involved in cell fate, polarity, tissue organization, and cilium and lumen formation. Here, we report the characterization of the intricate midbody protein-protein interaction network (interactome), which identifies many previously unknown interactions and provides an extremely valuable resource for dissecting the multiple roles of the midbody. Initial analysis of this interactome revealed that PP1β-MYPT1 phosphatase regulates microtubule dynamics in late cytokinesis and de-phosphorylates the kinesin component MKLP1/KIF23 of the centralspindlin complex. This de-phosphorylation antagonizes Aurora B kinase to modify the functions and interactions of centralspindlin in late cytokinesis. Our findings expand the repertoire of PP1 functions during mitosis and indicate that spatiotemporal changes in the distribution of kinases and counteracting phosphatases finely tune the activity of cytokinesis proteins. The midbody is an organelle present at the bridge connecting two cells at the end of cell division. Here, the authors use mass spectrometry to define the midbody interactome and uncover a role for PP1 phosphatases in microtubule dynamics and regulation of cytokinesis.