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Michael Glotzer - One of the best experts on this subject based on the ideXlab platform.

  • cortical recruitment of Centralspindlin and rhoa effectors during meiosis i of caenorhabditiselegans primary spermatocytes
    Journal of Cell Science, 2021
    Co-Authors: Xiangchuan Wang, Michael Glotzer, Dandan Zhang, Cunni Zheng, Yu Chung Tse
    Abstract:

    Haploid male gametes are produced through meiosis during gametogenesis. Whereas the cell biology of mitosis and meiosis is well studied in the nematode Caenorhabditis elegans, comparatively little is known regarding the physical division of primary spermatocytes during meiosis I. Here, we investigated this process by using high-resolution time-lapse confocal microscopy and examined the spatiotemporal regulation of contractile ring assembly in C. elegans primary spermatocytes. We found that Centralspindlin and RhoA effectors were recruited to the equatorial cortex of dividing primary spermatocytes for contractile ring assembly before segregation of homologous chromosomes. We also observed that perturbations shown to promote Centralspindlin oligomerization regulated the cortical recruitment of NMY-2 and impacted the order in which primary spermatocytes along the proximal distal axis of the gonad enter meiosis I. These results expand our understanding of the cellular division of primary spermatocytes into secondary spermatocytes during meiosis I.

  • PLK1 plays dual roles in Centralspindlin regulation during cytokinesis.
    The Journal of cell biology, 2019
    Co-Authors: Ingrid E. Adriaans, Michael Glotzer, Angika Basant, Bas Ponsioen, Susanne M.a. Lens
    Abstract:

    Cytokinesis begins upon anaphase onset. An early step involves local activation of the small GTPase RhoA, which triggers assembly of an actomyosin-based contractile ring at the equatorial cortex. Here, we delineated the contributions of PLK1 and Aurora B to RhoA activation and cytokinesis initiation in human cells. Knock-down of PRC1, which disrupts the spindle midzone, revealed the existence of two pathways that can initiate cleavage furrow ingression. One pathway depends on a well-organized spindle midzone and PLK1, while the other depends on Aurora B activity and Centralspindlin at the equatorial cortex and can operate independently of PLK1. We further show that PLK1 inhibition sequesters Centralspindlin onto the spindle midzone, making it unavailable for Aurora B at the equatorial cortex. We propose that PLK1 activity promotes the release of Centralspindlin from the spindle midzone through inhibition of PRC1, allowing Centralspindlin to function as a regulator of spindle midzone formation and as an activator of RhoA at the equatorial cortex.

  • PLK1 plays dual roles in Centralspindlin regulation during cytokinesis
    2018
    Co-Authors: Ingrid E. Adriaans, Michael Glotzer, Angika Basant, Bas Ponsioen, Susanne M.a. Lens
    Abstract:

    Cytokinesis starts in anaphase with the formation of an actomyosin-based contractile ring at the equatorial cortex, which is governed by the local activation of the small GTPase RhoA. Here we delineated the contributions of PLK1 and Aurora B to RhoA activation and cytokinesis initiation in human cells. Knock-down of PRC1, which disrupts the spindle midzone, revealed the existence of two pathways that can initiate cleavage furrow ingression. One pathway depends on a well-organized spindle midzone and PLK1, while the other depends on Aurora B activity and Centralspindlin oligomerization at the equatorial cortex and can operate independently of PLK1. We further show that PLK1 inhibition sequesters Centralspindlin onto the spindle midzone making it unavailable for Aurora B-dependent oligomerization at the equatorial cortex. We propose that PLK1 activity promotes the release of Centralspindlin from the spindle midzone through inhibition of PRC1, allowing Centralspindlin to function as a regulator of spindle midzone formation and as an activator of RhoA at the equatorial cortex.

  • Spatiotemporal Regulation of RhoA during Cytokinesis
    Current biology : CB, 2018
    Co-Authors: Angika Basant, Michael Glotzer
    Abstract:

    The active form of the small GTPase RhoA is necessary and sufficient for formation of a cytokinetic furrow in animal cells. Despite the conceptual simplicity of the process, the molecular mechanisms that control it are intricate and involve redundancy at multiple levels. Here, we discuss our current knowledge of the mechanisms underlying spatiotemporal regulation of RhoA during cytokinesis by upstream activators. The direct upstream activator, the RhoGEF Ect2, requires activation due to autoinhibition. Ect2 is primarily activated by the Centralspindlin complex, which contains numerous domains that regulate its subcellular localization, oligomeric state, and Ect2 activation. We review the functions of these domains and how Centralspindlin is regulated to ensure correctly timed, equatorial RhoA activation. Highlighting recent evidence, we propose that although Centralspindlin does not always prominently accumulate on the plasma membrane, it is the site where it promotes RhoA activation during cytokinesis.

  • A GAP that Divides.
    F1000Research, 2017
    Co-Authors: Angika Basant, Michael Glotzer
    Abstract:

    Cytokinesis in metazoan cells is mediated by an actomyosin-based contractile ring that assembles in response to activation of the small GTPase RhoA. The guanine nucleotide exchange factor that activates RhoA during cytokinesis, ECT-2, is highly regulated. In most metazoan cells, with the notable exception of the early Caenorhabditis elegans embryo, RhoA activation and furrow ingression require the Centralspindlin complex. This exception is due to the existence of a parallel pathway for RhoA activation in C. elegans . Centralspindlin contains CYK-4 which contains a predicted Rho family GTPase-activating protein (GAP) domain. The function of this domain has been the subject of considerable debate. Some publications suggest that the GAP domain promotes RhoA activation (for example, Zhang and Glotzer, 2015; Loria, Longhini and Glotzer, 2012), whereas others suggest that it functions to inactivate the GTPase Rac1 (for example, Zhuravlev et al ., 2017). Here, we review the mechanisms underlying RhoA activation during cytokinesis, primarily focusing on data in C. elegans. We highlight the importance of considering the parallel pathway for RhoA activation and detailed analyses of  cyk-4 mutant phenotypes when evaluating the role of the GAP domain of CYK-4.

Masanori Mishima - One of the best experts on this subject based on the ideXlab platform.

  • CYK4 relaxes the bias in the off-axis motion by MKLP1 kinesin-6
    Communications Biology, 2021
    Co-Authors: Yohei Maruyama, Masanori Mishima, Tim Davies, Mitsuhiro Sugawa, Shin Yamaguchi, Toshihisa Osaki, Takuya Kobayashi, Masahiko Yamagishi, Shoji Takeuchi, Junichiro Yajima
    Abstract:

    Centralspindlin, a complex of the MKLP1 kinesin-6 and CYK4 GAP subunits, plays key roles in metazoan cytokinesis. CYK4-binding to the long neck region of MKLP1 restricts the configuration of the two MKLP1 motor domains in the Centralspindlin. However, it is unclear how the CYK4-binding modulates the interaction of MKLP1 with a microtubule. Here, we performed three-dimensional nanometry of a microbead coated with multiple MKLP1 molecules on a freely suspended microtubule. We found that beads driven by dimeric MKLP1 exhibited persistently left-handed helical trajectories around the microtubule axis, indicating torque generation. By contrast, Centralspindlin, like monomeric MKLP1, showed similarly left-handed but less persistent helical movement with occasional rightward movements. Analysis of the fluctuating helical movement indicated that the MKLP1 stochastically makes off-axis motions biased towards the protofilament on the left. CYK4-binding to the neck domains in MKLP1 enables more flexible off-axis motion of Centralspindlin, which would help to avoid obstacles along crowded spindle microtubules. Analysing the 3D movement of MKLP1 motors, Maruyama et al. find that dimeric C. elegans MKLP1 drives a left-handed helical motion around the microtubule with minimum protofilament switching to the right side whereas less persistent motions are driven by monomers or by heterotetramers with CYK4. These findings suggest how obstacles along crowded spindle microtubules may be avoided by CYK4 binding to MKLP1.

  • preparation of Centralspindlin as an active heterotetramer of kinesin and gtpase activating protein subunits for in vitro structural and functional assays
    Methods in Cell Biology, 2017
    Co-Authors: Masanori Mishima
    Abstract:

    Centralspindlin is a crucial regulator of animal cytokinesis, consisting of MKLP1 kinesin-6 and CYK4 Rho-family GTPase activating protein (RhoGAP). As a microtubule-bundling protein, it plays a crucial role in the formation of the central spindle. Through distinct accumulation to the antiparallel microtubule overlaps at the central spindle and the midbody, it recruits various downstream factors to the site of cell division as well as anchors the plasma membrane to maintain the narrow intercellular channels between the daughter cells until their final separation (abscission). A unique and functionally important feature of Centralspindlin as a kinesin-containing protein complex is that the nonmotor component, CYK4, is not a passive cargo of the MKLP1 motor, but an integrated component of a microtubule-organizing machinery. Thus, for in vitro structural and functional assays, it is pivotal to prepare active stoichiometric complexes of the two components. Discussed here are two complimentary approaches, (1) reconstitution of the complex in bacterial extracts (in extract reconstitution) and (2) purification of a native complex from a mammalian cell line using a localization and affinity purification (LAP) tag.

  • Centralspindlin in Rappaport's cleavage signaling.
    Seminars in cell & developmental biology, 2016
    Co-Authors: Masanori Mishima
    Abstract:

    Cleavage furrow in animal cell cytokinesis is formed by cortical constriction driven by contraction of an actomyosin network activated by Rho GTPase. Although the role of the mitotic apparatus in furrow induction has been well established, there remain discussions about the detailed molecular mechanisms of the cleavage signaling. While experiments in large echinoderm embryos highlighted the role of astral microtubules, data in smaller cells indicate the role of central spindle. Centralspindlin is a constitutive heterotetramer of MKLP1 kinesin and the non-motor CYK4 subunit and plays crucial roles in formation of the central spindle and recruitment of the downstream cytokinesis factors including ECT2, the major activator of Rho during cytokinesis, to the site of division. Recent reports have revealed a role of this Centralspindlin-ECT2 pathway in furrow induction both by the central spindle and by the astral microtubules. Here, a unified view of the stimulation of cortical contractility by this pathway is discussed. Cytokinesis, the division of the whole cytoplasm, is an essential process for cell proliferation and embryonic development. In animal cells, cytokinesis is executed using a contractile network of actin filaments driven by a myosin-II motor that constricts the cell cortex (cleavage furrow ingression) into a narrow channel between the two daughter cells, which is resolved by scission (abscission) [1-3]. The anaphase-specific organization of the mitotic apparatus (MA, spindle with chromosomes plus asters) positions the cleavage furrow and plays a major role in spatial coupling between mitosis and cytokinesis [4-6]. The nucleus and chromosomes are dispensable for furrow specification [7-10], although they contribute to persistent furrowing and robust completion in some cell types [11,12]. Likewise, centrosomes are not essential for cytokinesis, but they contribute to the general fidelity of cell division [10,13-15]. Here, classical models of cleavage furrow induction are outlined, and a unified view of the stimulation of cortical contractility by the Centralspindlin-ECT2 pathway is discussed.

  • Central spindle robustness by PRC1-Centralspindlin interaction.
    Cell cycle (Georgetown Tex.), 2015
    Co-Authors: Masanori Mishima, Kianyong Lee
    Abstract:

    Mitotic apparatus (MA) plays central roles in cell division for both mitosis and cytokinesis. It achieves these mechanical tasks by changing its morphology under the control of cell cycle machinery. This relies on dynamic polymerization and depolymerization cycles of microtubules and their assembly into higher order structures such as bundles involving various microtubule regulators. A dramatic remodeling of the MA occurs at the metaphase to anaphase transition (Fig. 1). Before this, 2 spindle poles are connected both by interpolar microtubules and by kinetochore microtubules attaching the unsegregated chromatids. After anaphase onset, the link via kinetochore microtubules and chromosomes disappears due to loss of chromosome cohesion. As a consequence, the interpolar microtubules, which have now developed into a more prominent structure termed the central spindle, become the sole mechanical link between the 2 poles (Fig. 1, case i). Metaphase-anaphase transition also promotes the growth of astral microtubules. Dynein anchored at the cell cortex interacts with the astral microtubules and generates mechanical forces (cortical pulling forces) that pull spindle poles toward the cell cortex.1 Grill SW, et al. Nature 2001; 409(6820):630-3; PMID:11214323; http://dx.doi.org/10.1038/35054572 [CrossRef], [PubMed], [Web of Science ®] In some cell types such as the C. elegans embryos, cortical pulling force is the major driving force for chromosome separation via elongation of the pole-to-pole distance (anaphase B). In this situation, the central spindle is dispensable for chromosome segregation; it rather works as a brake against the cortical pulling force. Indeed, in C. elegans embryos, chromosome separation is accelerated when the central spindle is severed by laser manipulation or by genetic perturbation.2 Saunders AM, et al. Curr Biol 2007; 17(12):R453-4; PMID:17580072; http://dx.doi.org/10.1016/j.cub.2007.05.001 [CrossRef], [PubMed], [Web of Science ®] So, why does a cell form the central spindle? Well, this is because it has an important role in cytokinesis.

  • Direct interaction between Centralspindlin and PRC1 reinforces mechanical resilience of the central spindle
    Nature communications, 2015
    Co-Authors: Kianyong Lee, Behrooz Esmaeili, Ben Zealley, Masanori Mishima
    Abstract:

    During animal cell division, the central spindle, an anti-parallel microtubule bundle structure formed between segregating chromosomes during anaphase, cooperates with astral microtubules to position the cleavage furrow. Because the central spindle is the only structure linking the two halves of the mitotic spindle, it is under mechanical tension from dynein-generated cortical pulling forces, which determine spindle positioning and drive chromosome segregation through spindle elongation. The central spindle should be flexible enough for efficient chromosome segregation while maintaining its structural integrity for reliable cytokinesis. How the cell balances these potentially conflicting requirements is poorly understood. Here, we demonstrate that the central spindle in C. elegans embryos has a resilient mechanism for recovery from perturbations by excess tension derived from cortical pulling forces. This mechanism involves the direct interaction of two different types of conserved microtubule bundlers that are crucial for central spindle formation, PRC1 and Centralspindlin.

Mark Petronczki - One of the best experts on this subject based on the ideXlab platform.

  • Cell Division: Switching On ECT2 in a Non-Canonical Fashion
    Current biology : CB, 2020
    Co-Authors: Mark Petronczki, Antonio Tedeschi
    Abstract:

    Determining the site of cell cleavage is crucial for cytokinesis and involves precise activation of the RhoGEF ECT2. A new study demonstrates how a non-canonical interaction of ECT2 with Centralspindlin underlies cytokinesis in animal cells, solving a mechanistic conundrum.

  • Plasma Membrane Association but Not Midzone Recruitment of RhoGEF ECT2 Is Essential for Cytokinesis.
    Cell reports, 2016
    Co-Authors: Kristýna Kotýnková, Stephen C. West, Mark Petronczki
    Abstract:

    Cytokinesis, the final step of cell division, begins with the formation of a cleavage furrow. How the mitotic spindle specifies the furrow at the equator in animal cells remains unknown. Current models propose that the concentration of the RhoGEF ECT2 at the spindle midzone and the equatorial plasma membrane directs furrow formation. Using chemical genetic and optogenetic tools, we demonstrate that the association of ECT2 with the plasma membrane during anaphase is required and sufficient for cytokinesis. Local membrane targeting of ECT2 leads to unilateral furrowing, highlighting the importance of local ECT2 activity. ECT2 mutations that prevent Centralspindlin binding compromise concentration of ECT2 at the midzone and equatorial membrane but sustain cytokinesis. While the association of ECT2 with the plasma membrane is essential for cytokinesis, our data suggest that ECT2 recruitment to the spindle midzone is insufficient to account for equatorial furrowing and may act redundantly with yet-uncharacterized signals.

  • aurora b kinase promotes cytokinesis by inducing Centralspindlin oligomers that associate with the plasma membrane
    Developmental Cell, 2015
    Co-Authors: Angika Basant, Sergey Lekomtsev, Mark Petronczki, Yu Chung Tse, Donglei Zhang, Katrina M Longhini, Michael Glotzer
    Abstract:

    In metazoans, cytokinesis is triggered by activation of the GTPase RhoA at the equatorial plasma membrane. ECT-2, the guanine nucleotide exchange factor (GEF) required for RhoA activation, is activated by the Centralspindlin complex that concentrates on spindle midzone microtubules. However, these microtubules and the plasma membrane are not generally in apposition, and thus the mechanism by which RhoA is activated at the cell equator remains unknown. Here we report that a regulated pool of membrane-bound, oligomeric Centralspindlin stimulates RhoA activation. The membrane-binding C1 domain of CYK-4, a Centralspindlin component, promotes furrow initiation in C. elegans embryos and human cells. Membrane localization of Centralspindlin oligomers is globally inhibited by PAR-5/14-3-3. This activity is antagonized by the chromosome passenger complex (CPC), resulting in RhoA activation at the nascent cleavage site. Therefore, CPC-directed Centralspindlin oligomerization during anaphase induces contractile ring assembly at the membrane.

  • Centralspindlin links the mitotic spindle to the plasma membrane during cytokinesis
    Nature, 2012
    Co-Authors: Sergey Lekomtsev, Valerie E Pye, Ken Blight, Sriramkumar Sundaramoorthy, Tohru Takaki, Lucy M Collinson, Peter Cherepanov, Nullin Divecha, Mark Petronczki
    Abstract:

    At the end of cell division, cytokinesis splits the cytoplasm of nascent daughter cells and partitions segregated sister genomes. To coordinate cell division with chromosome segregation, the mitotic spindle controls cytokinetic events at the cell envelope. The spindle midzone stimulates the actomyosin-driven contraction of the cleavage furrow, which proceeds until the formation of a microtubule-rich intercellular bridge with the midbody at its centre. The midbody directs the final membrane abscission reaction and has been proposed to attach the cleavage furrow to the intercellular bridge. How the mitotic spindle is connected to the plasma membrane during cytokinesis is not understood. Here we identify a plasma membrane tethering activity in the Centralspindlin protein complex, a conserved component of the spindle midzone and midbody. We demonstrate that the C1 domain of the Centralspindlin subunit MgcRacGAP associates with the plasma membrane by interacting with polyanionic phosphoinositide lipids. Using X-ray crystallography we determine the structure of this atypical C1 domain. Mutations in the hydrophobic cap and in basic residues of the C1 domain of MgcRacGAP prevent association of the protein with the plasma membrane, and abrogate cytokinesis in human and chicken cells. Artificial membrane tethering of Centralspindlin restores cell division in the absence of the C1 domain of MgcRacGAP. Although C1 domain function is dispensable for the formation of the midzone and midbody, it promotes contractility and is required for the attachment of the plasma membrane to the midbody, a long-postulated function of this organelle. Our analysis suggests that Centralspindlin links the mitotic spindle to the plasma membrane to secure the final cut during cytokinesis in animal cells.

  • targeting of the rhogef ect2 to the equatorial membrane controls cleavage furrow formation during cytokinesis
    Developmental Cell, 2011
    Co-Authors: Kuanchung Su, Tohru Takaki, Mark Petronczki
    Abstract:

    Summary In animal cells, formation of the cytokinetic furrow requires activation of the GTPase RhoA by the guanine nucleotide exchange factor Ect2. How Ect2, which is associated with the spindle midzone, controls RhoA activity at the equatorial cortex during anaphase is not understood. Here, we show that Ect2 concentrates at the equatorial membrane during cytokinesis in live cells. Ect2 membrane association requires a pleckstrin homology domain and a polybasic cluster that bind to phosphoinositide lipids. Both guanine nucleotide exchange function and membrane targeting of Ect2 are essential for RhoA activation and cleavage furrow formation in human cells. Membrane localization of Ect2 is spatially confined to the equator by Centralspindlin, Ect2's spindle midzone anchor complex, and is temporally coordinated with chromosome segregation through the activation state of CDK1. We propose that targeting of Ect2 to the equatorial membrane represents a key step in the delivery of the cytokinetic signal to the cortex.

Alpha S. Yap - One of the best experts on this subject based on the ideXlab platform.

  • Centralspindlin and α-catenin regulate Rho signalling at the epithelial zonula adherens
    Nature Cell Biology, 2012
    Co-Authors: Aparna Ratheesh, Guillermo A. Gomez, Rashmi Priya, Suzie Verma, Eva M. Kovacs, Kai Jiang, Nicholas H. Brown, Anna Akhmanova, Samantha J. Stehbens, Alpha S. Yap
    Abstract:

    Yap and colleagues identify an extramitotic role for the Centralspindlin complex, a Rho signalling regulator during cytokinesis. They show that Centralspindlin interacts with α-catenin, and promotes epithelial junctional integrity by recruiting the ECT2 RhoGEF to the zonula adherens, as well as by inhibiting the junctional localization of the p190 B RhoGAP. The biological impact of Rho depends critically on the precise subcellular localization of its active, GTP-loaded form. This can potentially be determined by the balance between molecules that promote nucleotide exchange or GTP hydrolysis. However, how these activities may be coordinated is poorly understood. We now report a molecular pathway that achieves exactly this coordination at the epithelial zonula adherens. We identify an extramitotic activity of the Centralspindlin complex, better understood as a cytokinetic regulator, which localizes to the interphase zonula adherens by interacting with the cadherin-associated protein, α-catenin. Centralspindlin recruits the RhoGEF, ECT2, to activate Rho and support junctional integrity through myosin IIA. Centralspindlin also inhibits the junctional localization of p190 B RhoGAP, which can inactivate Rho. Thus, a conserved molecular ensemble that governs Rho activation during cytokinesis is used in interphase cells to control the Rho GTPase cycle at the zonula adherens.

  • Centralspindlin and α-catenin regulate Rho signalling at the epithelial zonula adherens
    2012
    Co-Authors: Aparna Ratheesh, Guillermo A. Gomez, Rashmi Priya, Suzie Verma, Eva M. Kovacs, Kai Jiang, Nicholas H. Brown, Anna Akhmanova, Samantha J. Stehbens, Alpha S. Yap
    Abstract:

    The biological impact of Rho depends critically on the precise subcellular localization of its active, GTP-loaded form. This can potentially be determined by the balance between molecules that promote nucleotide exchange or GTP hydrolysis. However, how these activities may be coordinated is poorly understood. We now report a molecular pathway that achieves exactly this coordination at the epithelial zonula adherens. We identify an extramitotic activity of the Centralspindlin complex, better understood as a cytokinetic regulator, which localizes to the interphase zonula adherens by interacting with the cadherin-associated protein, α-catenin. Centralspindlin recruits the RhoGEF, ECT2, to activate Rho and support junctional integrity through myosin IIA. Centralspindlin also inhibits the junctional localization of p190 B RhoGAP, which can inactivate Rho. Thus, a conserved molecular ensemble that governs Rho activation during cytokinesis is used in interphase cells to control the Rho GTPase cycle at the zonula adherens

David M Glover - One of the best experts on this subject based on the ideXlab platform.

  • JCB: Article Nessun Dorma, a novel Centralspindlin partner, is required for cytokinesis in Drosophila spermatocytes
    2013
    Co-Authors: Emilie Montembault, Wei Zhang, Marcin R Przewloka, Vincent Archambault, Emeric W Sevin, Ernest D Laue, David M Glover, Pier Paolo D’avino
    Abstract:

    Cytokinesis, the final step of cell division, usually ends with the abscission of the two daughter cells. In some tissues, however, daughter cells never completely separate and remain interconnected by intercellular bridges or ring canals. In this paper, we report the identification and analysis of a novel ring canal component, Nessun Dorma (Nesd), isolated as an evolutionarily conserved partner of the Centralspindlin complex, a key regulator of cytokinesis. Nesd contains a pectin lyase–lik

  • nessun dorma a novel Centralspindlin partner is required for cytokinesis in drosophila spermatocytes
    Journal of Cell Biology, 2010
    Co-Authors: Emilie Montembault, Wei Zhang, Marcin R Przewloka, Vincent Archambault, Emeric W Sevin, Ernest D Laue, David M Glover, Pier Paolo Davino
    Abstract:

    Cytokinesis, the final step of cell division, usually ends with the abscission of the two daughter cells. In some tissues, however, daughter cells never completely separate and remain interconnected by intercellular bridges or ring canals. In this paper, we report the identification and analysis of a novel ring canal component, Nessun Dorma (Nesd), isolated as an evolutionarily conserved partner of the Centralspindlin complex, a key regulator of cytokinesis. Nesd contains a pectin lyase–like domain found in proteins that bind to polysaccharides, and we present evidence that it has high affinity for β-galactosides in vitro. Moreover, nesd is an essential gene in Drosophila melanogaster, in which it is required for completion of cytokinesis during male meiosis and possibly in female germline cells. Our findings indicate that Nesd is a novel carbohydrate-binding protein that functions together with Centralspindlin in late cytokinesis, thus highlighting the importance of glycosylation in this process.

  • Cytokinesis: mind the GAP
    Nature Cell Biology, 2009
    Co-Authors: Pier Paolo D'avino, David M Glover
    Abstract:

    Cytokinesis ensures proper partitioning of genomic and cytoplasmic material between dividing cells. A key regulator of this process is the Centralspindlin complex. Two recent papers report that GAP activity of one of the members of this complex regulates the function of Rho family GTPases during cytokinesis.

  • RacGAP50C is sufficient to signal cleavage furrow formation during cytokinesis.
    Journal of cell science, 2006
    Co-Authors: Pier Paolo D'avino, Matthew S Savoian, Luisa Capalbo, David M Glover
    Abstract:

    Several studies indicate that spindle microtubules determine the position of the cleavage plane at the end of cell division, but their exact role in triggering the formation and ingression of the cleavage furrow is still unclear. Here we show that in Drosophila depletion of either the GAP (GTPase-activating protein) or the kinesin-like subunit of the evolutionary conserved Centralspindlin complex prevents furrowing without affecting the association of astral microtubules with the cell cortex. Moreover, time-lapse imaging indicates that astral microtubules serve to deliver the Centralspindlin complex to the equatorial cortex just before furrow formation. However, when the GAP-signaling component was mislocalized around the entire cortex using a membrane-tethering motif, this caused ectopic furrowing even in the absence of its motor partner. Thus, the GAP component of Centralspindlin is both necessary and sufficient for furrow formation and ingression and astral microtubules provide a route for its delivery to the cleavage site.

  • Cleavage furrow formation and ingression during animal cytokinesis: a microtubule legacy.
    Journal of Cell Science, 2005
    Co-Authors: Pier Paolo D'avino, Matthew S Savoian, David M Glover
    Abstract:

    Cytokinesis ensures the proper partitioning of the nuclear and cytoplasmic contents into independent daughter cells at the end of cell division. Although the metazoan mitotic spindle has been implicated in the placement and advancement of the cleavage furrow, the molecules responsible for these processes have remained elusive. Recent studies have provided insights into the role of different microtubule structures and associated proteins in cleavage furrow positioning and ingression together with the signalling events that regulate the dynamics of the equatorial cell cortex during cytokinesis. We try to unify these findings into a general model of cytokinesis in which both astral and central spindle microtubules have the ability to induce furrowing. We further propose that the evolutionarily conserved Centralspindlin complex serves as a master controller of cell cleavage in Drosophila by promoting both furrow formation and ingression. The same mechanism might be conserved in other organisms.