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Rho proteins the key regulators of cytoskeleton in the progression of mitosis and cytokinesis
Anna Klimaszewska,Anna Stenzel,Jakub Marcin Nowak,Alina Grzanka
Post?py Higieny i Medycyny Do?wiadczalnej , 2011,
Abstract: The Rho proteins are members of the Ras superfamily of small GTPases. They are thought to be crucial regulators of multiple signal transduction pathways that influence a wide range of cellular functions, including migration, membrane trafficking, adhesion, polarity and cell shape changes. Thanks to their ability to control the assembly and organization of the actin and microtubule cytoskeletons, Rho GTPases are known to regulate mitosis and cytokinesis progression. These proteins are required for formation and rigidity of the cortex during mitotic cell rounding, mitotic spindle formation and attachment of the spindle microtubules to the kinetochore. In addition, during cytokinesis, they are involved in promoting division plane determination, contractile ring and cleavage furrow formation and abscission. They are also known as regulators of cell cycle progression at the G1/S and G2/M transition. Thus, the signal transduction pathways in which Rho proteins participate, appear to connect dynamics of actin and microtubule cytoskeletons to cell cycle progression. We review the current state of knowledge concerning the molecular mechanisms by which Rho GTPase signaling regulates remodeling of actin and microtubule cytoskeletons in order to control cell division progression.
Roles for microtubule and microfilament cytoskeletons in animal cell cytokinesis
Zhongcai Chen,Shang Cai,Qing Jiang,Chuanmao Zhang,Xiaowei Tang
Chinese Science Bulletin , 2005, DOI: 10.1007/BF02897532
Abstract: Microtubule and microfilament cytoskeletons play key roles in the whole process of cytokinesis. Although a number of hypotheses have been proposed to elucidate the mechanism of cytokinesis by microtubule and actin filament cytoskeletons, many reports are conflicting. In our study, combining the cytoskeletons drug treatments with the time-lapse video technology, we retested the key roles of microtubule and actin filament in cytokinesis. The results showed that depolymerization of microtubules by Nocodazole after the initiation of furrowing would not inhibit the furrow ingression, but obviously decrease the stiffness of daughter cells. Depolymerizing actin filaments by Cytochalasin B before metaphase would inhibit the initiation of furrowing but not chromosome segregation, resulting in the formation of binucleate cells; however, depolymerizing actin filaments during anaphase would prevent furrowing and lead to the regress of established furrow, also resulting in the formation of binucleate cells. Further, depolymerizing microtubules and actin filaments simultaneously after metaphase would cause the quick regress of the furrow and the formation of binucleate cells. From these results we propose that a successful cytokinesis requires functions and coordination of both the microtubule and actin filament cytoskeletons. Microtubule cytoskeleton may function in the positioning and initiation of cleavage furrow, and the actin filament cytoskeleton may play key roles in the initiation and ingression of the furrow.
Roles for microtubule and microfilament cytoskeletons in animal cell cytokinesis
CHEN Zhongcai?,CAI Shang,JIANG Qing,ZHANG Chuanmao & TANG Xiaowei Institute of High Energy Physics,Chinese Academy of Sciences,Bei- jing,China,National Laboratory of Biomembrane,Membrane Biotechnology,
CHENZhongcai
,CAIShang,JIANGQing,ZHANGChuanmao,TANGXiaowei

科学通报(英文版) , 2005,
Abstract: Microtubule and microfilament cytoskeletons play key roles in the whole process of cytokinesis. Although a number of hypotheses have been proposed to elucidate the mechanism of cytokinesis by microtubule and actin filament cytoskeletons, many reports are conflicting. In our study, combining the cytoskeletons drug treatments with the time-lapse video technology, we retested the key roles of microtubule and actin filament in cytokinesis. The results showed that depolymerization of microtubules by Nocoda- zole after the initiation of furrowing would not inhibit the furrow ingression, but obviously decrease the stiffness of daughter cells. Depolymerizing actin filaments by Cyto- chalasin B before metaphase would inhibit the initiation of furrowing but not chromosome segregation, resulting in the formation of binucleate cells; however, depolymerizing actin filaments during anaphase would prevent furrowing and lead to the regress of established furrow, also resulting in the formation of binucleate cells. Further, depolymerizing microtubules and actin filaments simultaneously after meta- phase would cause the quick regress of the furrow and the formation of binucleate cells. From these results we propose that a successful cytokinesis requires functions and coordina- tion of both the microtubule and actin filamentcytoskeletons. Microtubule cytoskeleton may function in the positioning and initiation of cleavage furrow, and the actin filament cy- toskeleton may play key roles in the initiation and ingression of the furrow.
Theoretical Models of Cytokinesis and Mitosis (Without Asters)
Kang Cheng,Changhua Zou
American Journal of Plant Physiology , 2006,
Abstract: What cause the mitosis (without asters) and cytokinesis for normal higher plant cells is a question that has never been answered quantitatively and theoretically according to our knowledge. In this study, based on published experimental data, Newton`s laws and Coulomb`s law, we develop novel theoretical models of natural and normal mitosis (without asters) and cytokinesis for higher plant cells in M phase, to dynamically explicit several movements of biological objects (chromosomes, the spindle poles and microtubules). We hypothesize for wild types of higher plant cells: 1, No naturally and normally replicated chromosomes can occupy the same nucleus, without growing sizes of the nucleus and the cell (Chromosomes Exclusion); 2, No normally and naturally doubled nuclei can occupy the same cell, if the doubled size of the nuclei is not far smaller than the size of the cell (Nuclei Exclusion); 3, The spontaneous and strong repulsive electromagnetic field forces are the primary cause for the exclusions.
Genetic Deletion of SEPT7 Reveals a Cell Type-Specific Role of Septins in Microtubule Destabilization for the Completion of Cytokinesis  [PDF]
Manoj B. Menon ,Akihiro Sawada,Anuhar Chaturvedi,Pooja Mishra,Karin Schuster-Gossler,Melanie Galla,Axel Schambach,Achim Gossler,Reinhold F?rster,Michael Heuser,Alexey Kotlyarov,Makoto Kinoshita ,Matthias Gaestel
PLOS Genetics , 2014, DOI: doi/10.1371/journal.pgen.1004558
Abstract: Cytokinesis terminates mitosis, resulting in separation of the two sister cells. Septins, a conserved family of GTP-binding cytoskeletal proteins, are an absolute requirement for cytokinesis in budding yeast. We demonstrate that septin-dependence of mammalian cytokinesis differs greatly between cell types: genetic loss of the pivotal septin subunit SEPT7 in vivo reveals that septins are indispensable for cytokinesis in fibroblasts, but expendable in cells of the hematopoietic system. SEPT7-deficient mouse embryos fail to gastrulate, and septin-deficient fibroblasts exhibit pleiotropic defects in the major cytokinetic machinery, including hyperacetylation/stabilization of microtubules and stalled midbody abscission, leading to constitutive multinucleation. We identified the microtubule depolymerizing protein stathmin as a key molecule aiding in septin-independent cytokinesis, demonstrated that stathmin supplementation is sufficient to override cytokinesis failure in SEPT7-null fibroblasts, and that knockdown of stathmin makes proliferation of a hematopoietic cell line sensitive to the septin inhibitor forchlorfenuron. Identification of septin-independent cytokinesis in the hematopoietic system could serve as a key to identify solid tumor-specific molecular targets for inhibition of cell proliferation.
The role of MEN (mitosis exit network) proteins in the cytokinesis of Saccharomyces cerevisiae
Jiménez,Javier; Castelao,Beatriz A.; González-Novo,Alberto; Sánchez-Pérez,Miguel;
International Microbiology , 2005,
Abstract: at the latest stages of their cell cycle, cells carry out crucial processes for the correct segregation of their genetic and cytoplasmic material. in this work, we provide evidence demonstrating that the cell cycle arrest of some men (mitosis exit network) mutants in the anaphase-telophase transition is bypassed. in addition, the ability of cdc15 diploid mutant strains to develop non-septated chains of cells, supported by nuclear division, is shown. this phenotype is also displayed by haploid cdc15 mutant strains when cell lysis is prevented by osmotic protection, and shared by other men mutants. by contrast, anaphase-telophase arrest is strictly observed in double men-fear (fourteen early anaphase release) mutants. in this context, the overexpression of a fear component, spo12, in a men mutant background enhances the ability of men mutants to bypass cell cycle arrest. taken together, these data suggest a critical role of cdc15 and other men proteins in cytokinesis, allowing a new model for their cellular function to be proposed.
Katanin p60 Contributes to Microtubule Instability around the Midbody and Facilitates Cytokinesis in Rat Cells  [PDF]
Moe Matsuo, Tetsuhiro Shimodaira, Takashi Kasama, Yukie Hata, Ayumi Echigo, Masaki Okabe, Kazuya Arai, Yasutaka Makino, Shin-Ichiro Niwa, Hideyuki Saya, Toshihiko Kishimoto
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0080392
Abstract: The completion of cytokinesis is crucial for mitotic cell division. Cleavage furrow ingression is followed by the breaking and resealing of the intercellular bridge, but the detailed mechanism underlying this phenomenon remains unknown. Katanin is a microtubule-severing protein comprised of an AAA ATPase subunit and an accessory subunit designated as p60 and p80, respectively. Localization of katanin p60 was observed at the midzone to midbody from anaphase to cytokinesis in rat cells, and showed a ring-shaped distribution in the gap between the inside of the contractile ring and the central spindle bundle in telophase. Katanin p60 did not bind with p80 at the midzone or midbody, and localization was shown to be dependent on microtubules. At the central spindle and the midbody, no microtubule growth plus termini were seen with katanin p60, and microtubule density was inversely correlated with katanin p60 density in the region of katanin p60 localization that seemed to lead to microtubule destabilization at the midbody. Inhibition of katanin p60 resulted in incomplete cytokinesis by regression and thus caused the appearance of binucleate cells. These results suggest that katanin p60 contributes to microtubule instability at the midzone and midbody and facilitates cytokinesis in rat cells.
The Chromosomal Passenger Complex and a Mitotic Kinesin Interact with the Tousled-Like Kinase in Trypanosomes to Regulate Mitosis and Cytokinesis  [PDF]
Ziyin Li, Takashi Umeyama, Ching C. Wang
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0003814
Abstract: Aurora B kinase plays essential roles in mitosis and cytokinesis in eukaryotes. In the procyclic form of Trypanosoma brucei, the Aurora B homolog TbAUK1 regulates mitosis and cytokinesis, phosphorylates the Tousled-like kinase TbTLK1, interacts with two mitotic kinesins TbKIN-A and TbKIN-B and forms a novel chromosomal passenger complex (CPC) with two novel proteins TbCPC1 and TbCPC2. Here we show with time-lapse video microscopy the time course of CPC trans-localization from the spindle midzone in late anaphase to the dorsal side of the cell where the anterior end of daughter cell is tethered, and followed by a glide toward the posterior end to divide the cell, representing a novel mode of cytokinesis in eukaryotes. The three subunits of CPC, TbKIN-B and TbTLK1 interact with one another suggesting a close association among the five proteins. An ablation of TbTLK1 inhibited the subsequent trans-localization of CPC and TbKIN-B, whereas a knockdown of CPC or TbKIN-B disrupted the spindle pole localization of TbTLK1 during mitosis. In the bloodstream form of T. brucei, the five proteins also play essential roles in chromosome segregation and cytokinesis and display subcellular localization patterns similar to that in the procyclic form. The CPC in bloodstream form also undergoes a trans-localization during cytokinesis similar to that in the procyclic form. All together, our results indicate that the five-protein complex CPC-TbTLK1-TbKIN-B plays key roles in regulating chromosome segregation in the early phase of mitosis and that the highly unusual mode of cytokinesis mediated by CPC occurs in both forms of trypanosomes.
A Microtubule Interactome: Complexes with Roles in Cell Cycle and Mitosis  [PDF]
Julian R. Hughes,Ana M. Meireles,Katherine H. Fisher,Angel Garcia,Philip R. Antrobus,Alan Wainman,Nicole Zitzmann,Charlotte Deane,Hiroyuki Ohkura,James G. Wakefield
PLOS Biology , 2012, DOI: 10.1371/journal.pbio.0060098
Abstract: The microtubule (MT) cytoskeleton is required for many aspects of cell function, including the transport of intracellular materials, the maintenance of cell polarity, and the regulation of mitosis. These functions are coordinated by MT-associated proteins (MAPs), which work in concert with each other, binding MTs and altering their properties. We have used a MT cosedimentation assay, combined with 1D and 2D PAGE and mass spectrometry, to identify over 250 MAPs from early Drosophila embryos. We have taken two complementary approaches to analyse the cellular function of novel MAPs isolated using this approach. First, we have carried out an RNA interference (RNAi) screen, identifying 21 previously uncharacterised genes involved in MT organisation. Second, we have undertaken a bioinformatics analysis based on binary protein interaction data to produce putative interaction networks of MAPs. By combining both approaches, we have identified and validated MAP complexes with potentially important roles in cell cycle regulation and mitosis. This study therefore demonstrates that biologically relevant data can be harvested using such a multidisciplinary approach, and identifies new MAPs, many of which appear to be important in cell division.
A Microtubule Interactome: Complexes with Roles in Cell Cycle and Mitosis  [PDF]
Julian R Hughes equal contributor,Ana M Meireles equal contributor,Katherine H Fisher equal contributor,Angel Garcia,Philip R Antrobus,Alan Wainman,Nicole Zitzmann,Charlotte Deane,Hiroyuki Ohkura,James G Wakefield
PLOS Biology , 2008, DOI: 10.1371/journal.pbio.0060098
Abstract: The microtubule (MT) cytoskeleton is required for many aspects of cell function, including the transport of intracellular materials, the maintenance of cell polarity, and the regulation of mitosis. These functions are coordinated by MT-associated proteins (MAPs), which work in concert with each other, binding MTs and altering their properties. We have used a MT cosedimentation assay, combined with 1D and 2D PAGE and mass spectrometry, to identify over 250 MAPs from early Drosophila embryos. We have taken two complementary approaches to analyse the cellular function of novel MAPs isolated using this approach. First, we have carried out an RNA interference (RNAi) screen, identifying 21 previously uncharacterised genes involved in MT organisation. Second, we have undertaken a bioinformatics analysis based on binary protein interaction data to produce putative interaction networks of MAPs. By combining both approaches, we have identified and validated MAP complexes with potentially important roles in cell cycle regulation and mitosis. This study therefore demonstrates that biologically relevant data can be harvested using such a multidisciplinary approach, and identifies new MAPs, many of which appear to be important in cell division.
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