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Small GTPases Jan 2022Cytokinesis is required to cleave the daughter cells at the end of mitosis and relies on the spatiotemporal control of RhoA GTPase. Cytokinesis failure can lead to... (Review)
Review
Cytokinesis is required to cleave the daughter cells at the end of mitosis and relies on the spatiotemporal control of RhoA GTPase. Cytokinesis failure can lead to changes in cell fate or aneuploidy, which can be detrimental during development and/or can lead to cancer. However, our knowledge of the pathways that regulate RhoA during cytokinesis is limited, and the role of other Rho family GTPases is not clear. This is largely because the study of Rho GTPases presents unique challenges using traditional cell biological and biochemical methods, and they have pleiotropic functions making genetic studies difficult to interpret. The recent generation of optogenetic tools and biosensors that control and detect active Rho has overcome some of these challenges and is helping to elucidate the role of RhoA in cytokinesis. However, improvements are needed to reveal the role of other Rho GTPases in cytokinesis, and to identify the molecular mechanisms that control Rho activity. This review examines some of the outstanding questions in cytokinesis, and explores tools for the imaging and control of Rho GTPases.
Topics: Cytokinesis; rho GTP-Binding Proteins; Mitosis
PubMed: 34405757
DOI: 10.1080/21541248.2021.1957384 -
FEMS Microbiology Reviews Mar 2014The actin cytoskeleton is a complex network of dynamic polymers, which plays an important role in various fundamental cellular processes, including maintenance of cell... (Review)
Review
The actin cytoskeleton is a complex network of dynamic polymers, which plays an important role in various fundamental cellular processes, including maintenance of cell shape, polarity, cell division, cell migration, endocytosis, vesicular trafficking, and mechanosensation. Precise spatiotemporal assembly and disassembly of actin structures is regulated by the coordinated activity of about 100 highly conserved accessory proteins, which nucleate, elongate, cross-link, and sever actin filaments. Both in vivo studies in a wide range of organisms from yeast to metazoans and in vitro studies of purified proteins have helped shape the current understanding of actin dynamics and function. Molecular genetics, genome-wide functional analysis, sophisticated real-time imaging, and ultrastructural studies in concert with biochemical analysis have made yeast an attractive model to understand the actin cytoskeleton, its molecular dynamics, and physiological function. Studies of the yeast actin cytoskeleton have contributed substantially in defining the universal mechanism regulating actin assembly and disassembly in eukaryotes. Here, we review some of the important insights generated by the study of actin cytoskeleton in two important yeast models the budding yeast Saccharomyces cerevisiae and the fission yeast Schizosaccharomyces pombe.
Topics: Actin Cytoskeleton; Cell Polarity; Cytokinesis; Endocytosis; Saccharomyces cerevisiae; Schizosaccharomyces
PubMed: 24467403
DOI: 10.1111/1574-6976.12064 -
Cells Nov 2022Cytokinesis, the conclusive act of cell division, allows cytoplasmic organelles and chromosomes to be faithfully partitioned between two daughter cells. In animal... (Review)
Review
Cytokinesis, the conclusive act of cell division, allows cytoplasmic organelles and chromosomes to be faithfully partitioned between two daughter cells. In animal organisms, its accurate regulation is a fundamental task for normal development and for preventing aneuploidy. Cytokinesis failures produce genetically unstable tetraploid cells and ultimately result in chromosome instability, a hallmark of cancer cells. In animal cells, the assembly and constriction of an actomyosin ring drive cleavage furrow ingression, resulting in the formation of a cytoplasmic intercellular bridge, which is severed during abscission, the final event of cytokinesis. Kinase-mediated phosphorylation is a crucial process to orchestrate the spatio-temporal regulation of the different stages of cytokinesis. Several kinases have been described in the literature, such as cyclin-dependent kinase, polo-like kinase 1, and Aurora B, regulating both furrow ingression and/or abscission. However, others exist, with well-established roles in cell-cycle progression but whose specific role in cytokinesis has been poorly investigated, leading to considering these kinases as "minor" actors in this process. Yet, they deserve additional attention, as they might disclose unexpected routes of cell division regulation. Here, we summarize the role of multifunctional kinases in cytokinesis with a special focus on those with a still scarcely defined function during cell cleavage. Moreover, we discuss their implication in cancer.
Topics: Animals; Cytokinesis; Actomyosin; Cell Division; Phosphorylation; Actin Cytoskeleton
PubMed: 36429067
DOI: 10.3390/cells11223639 -
The Plant Cell Jan 2022The field of plant cell biology has a rich history of discovery, going back to Robert Hooke's discovery of cells themselves. The development of microscopes and... (Review)
Review
The field of plant cell biology has a rich history of discovery, going back to Robert Hooke's discovery of cells themselves. The development of microscopes and preparation techniques has allowed for the visualization of subcellular structures, and the use of protein biochemistry, genetics, and molecular biology has enabled the identification of proteins and mechanisms that regulate key cellular processes. In this review, seven senior plant cell biologists reflect on the development of this research field in the past decades, including the foundational contributions that their teams have made to our rich, current insights into cell biology. Topics covered include signaling and cell morphogenesis, membrane trafficking, cytokinesis, cytoskeletal regulation, and cell wall biology. In addition, these scientists illustrate the pathways to discovery in this exciting research field.
Topics: Cell Biology; Cell Wall; Cytokinesis; Cytoskeleton; Plant Cells; Plant Physiological Phenomena; Signal Transduction
PubMed: 34524464
DOI: 10.1093/plcell/koab234 -
Current Biology : CB Apr 2018Cells don't simply separate at cytokinesis. While furrow contraction critically relies on myosin-II and F-actin, post-furrowing steps are less understood but involve the... (Review)
Review
Cells don't simply separate at cytokinesis. While furrow contraction critically relies on myosin-II and F-actin, post-furrowing steps are less understood but involve the constriction of ESCRT-III polymer-dependent helices on the side of the midbody, which likely drive final abscission. The first evidence that animal cell cytokinesis requires membrane traffic, as in plant cells, was provided about 15 years ago. Since then, it has become increasingly clear that fusion of vesicles to the cytokinetic furrow is essential in large embryonic cells, and that membrane traffic within the intercellular bridge is crucial for its stability and successful abscission in all animal cells. Here, we review our current knowledge of the secretory and endocytic recycling pathways involved in cytokinesis, and how vesicles defined by specific Rab and Arf GTPases are targeted and fused to the membrane of the intercellular bridge thanks to different molecular motors, tethering complexes and SNARE machineries. At the functional level, we will describe how membrane traffic can remodel both phosphoinositide lipids and promote F-actin clearance necessary for ESCRT-III-dependent abscission, and identify key unanswered questions in the field. We will finally review recent evidence showing a tight coupling between membrane traffic and cytokinesis in complex processes, such as during the establishment of de novo apico-basal polarity.
Topics: Actin Cytoskeleton; Actins; Animals; Biological Transport; Cell Membrane; Cytokinesis; Endosomal Sorting Complexes Required for Transport; GTP Phosphohydrolases; Humans; Protein Transport
PubMed: 29689230
DOI: 10.1016/j.cub.2018.01.019 -
Autophagy Oct 2013A fundamental issue in cell biology is how the activation of a signaling pathway should lead to the appropriate cell response. Because of their oncogenic potential, the... (Review)
Review
A fundamental issue in cell biology is how the activation of a signaling pathway should lead to the appropriate cell response. Because of their oncogenic potential, the abundance, the duration and the localization of key signaling proteins must be carefully controlled. Negative feedback loops that combine transcription and protein-protein interactions are among the strategies by which a cell can turn off signaling. Our recent studies in Cancer Research and Autophagy show that degradation of key active proteins such as RHOA-GTP by constitutive autophagy represents one safeguard mechanism that limits signaling in a spatially and temporally restricted manner for faithful cytokinesis and directed migration. As a result, all autophagy compromises drive cytokinesis failure, aneuploidy, and motility-three processes that directly have an impact upon cancer progression. We therefore propose the term "signalphagy" to indicate a dedicated type of macroautophagy that degrades and thereby maintains the appropriate level of active signaling proteins to achieve tumor suppression.
Topics: Animals; Autophagy; Cell Movement; Cytokinesis; Humans; Intracellular Signaling Peptides and Proteins; Signal Transduction; rhoA GTP-Binding Protein
PubMed: 24004837
DOI: 10.4161/auto.25880 -
Nature Reviews. Molecular Cell Biology Feb 2015The appropriate timing of events that lead to chromosome segregation during mitosis and cytokinesis is essential to prevent aneuploidy, and defects in these processes... (Review)
Review
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.
Topics: Anaphase-Promoting Complex-Cyclosome; Cell Cycle Proteins; Chromosome Segregation; Cytokinesis; Humans; Mitosis
PubMed: 25604195
DOI: 10.1038/nrm3934 -
The Journal of Cell Biology Oct 2017Experiments on model systems have revealed that cytokinesis in cells with contractile rings (amoebas, fungi, and animals) depends on shared molecular mechanisms in spite... (Review)
Review
Experiments on model systems have revealed that cytokinesis in cells with contractile rings (amoebas, fungi, and animals) depends on shared molecular mechanisms in spite of some differences that emerged during a billion years of divergent evolution. Understanding these fundamental mechanisms depends on identifying the participating proteins and characterizing the mechanisms that position the furrow, assemble the contractile ring, anchor the ring to the plasma membrane, trigger ring constriction, produce force to form a furrow, disassemble the ring, expand the plasma membrane in the furrow, and separate the daughter cell membranes. This review reveals that fascinating questions remain about each step.
Topics: Amoeba; Animals; Biological Evolution; Cell Membrane; Cytokinesis; Fungi; Humans
PubMed: 28807993
DOI: 10.1083/jcb.201612068 -
The EMBO Journal Nov 2023During mitosis, spindle architecture alters as chromosomes segregate into daughter cells. The microtubule crosslinker protein regulator of cytokinesis 1 (PRC1) is...
During mitosis, spindle architecture alters as chromosomes segregate into daughter cells. The microtubule crosslinker protein regulator of cytokinesis 1 (PRC1) is essential for spindle stability, chromosome segregation and completion of cytokinesis, but how it recruits motors to the central spindle to coordinate the segregation of chromosomes is unknown. Here, we combine structural and cell biology approaches to show that the human CENP-E motor, which is essential for chromosome capture and alignment by microtubules, binds to PRC1 through a conserved hydrophobic motif. This binding mechanism is also used by Kinesin-4 Kif4A:PRC1. Using in vitro reconstitution, we demonstrate that CENP-E slides antiparallel PRC1-crosslinked microtubules. We find that the regulation of CENP-E -PRC1 interaction is spatially and temporally coupled with relocalization to overlapping microtubules in anaphase. Finally, we demonstrate that the PRC1-microtubule motor interaction is essential in anaphase to control chromosome partitioning, retain central spindle integrity and ensure cytokinesis. Taken together our findings reveal the molecular basis for the cell cycle regulation of motor-PRC1 complexes to couple chromosome segregation and cytokinesis.
Topics: Humans; Cytokinesis; Kinesins; Phosphorylation; Spindle Apparatus; Mitosis; Cell Cycle Proteins; Microtubules
PubMed: 37592895
DOI: 10.15252/embj.2023113647 -
The Journal of Cell Biology Mar 2022During cytokinesis, microtubules become compacted into a dense midbody prior to abscission. Using genetic perturbations and imaging of C. elegans zygotes, Hirsch et al....
During cytokinesis, microtubules become compacted into a dense midbody prior to abscission. Using genetic perturbations and imaging of C. elegans zygotes, Hirsch et al. (2022. J. Cell Biol.https://doi.org/10.1083/jcb.202011085) uncover an unexpected source of microtubules that can populate the midbody when central spindle microtubules are missing.
Topics: Animals; Caenorhabditis elegans; Cytokinesis; Microtubules
PubMed: 35191950
DOI: 10.1083/jcb.202201028