Involvement of IQGAP family proteins in the regulation of mammalian cell cytokinesis

IQGAP family proteins, comprising IQGAP1, ‐2, and ‐3 in mammals, are involved in diverse ranges of cellular processes such as adhesion and migration. IQGAP proteins in yeast also play important roles in cytokinesis. However, the involvement of IQGAP proteins in cytokinesis in mammals remains unaddressed. In this study, we showed that IQGAP3 specifically localized to the equatorial cortex at anaphase, whereas IQGAP1 localized to the cell cortex uniformly and IQGAP2 was unexpressed in HeLa cells. IQGAP3, but neither IQGAP1 nor ‐2, was able to interact with anillin, which was required for the localization of IQGAP3 to the contractile ring. The suppressed expression of IQGAP3 inhibited the completion of cleavage furrow ingression and led to the multinucleation of cells. The suppression of IQGAP1 also had similar inhibitory effects on cytokinesis, and the simultaneous suppression of IQGAP1 and ‐3 induced more severe effects. The localization of anillin and RhoA to the contractile ring was impaired by the suppression of IQGAP1 and ‐3, whereas their upstream regulators, the centralspindlin complex and Ect2, remained unaffected. These results suggested that mammalian IQGAP proteins may play a role in cytokinesis by regulating the localization of key cytokinesis regulatory proteins to the contractile apparatus during mitosis.

[1]  M. Petronczki,et al.  Cytokinesis in animal cells. , 2015, Cold Spring Harbor perspectives in biology.

[2]  J. Canman,et al.  Rho GTPases in animal cell cytokinesis: An occupation by the one percent , 2012, Cytoskeleton.

[3]  Erin A. White,et al.  Centralspindlin: At the heart of cytokinesis , 2012, Cytoskeleton.

[4]  Clemens Cabernard Cytokinesis in Drosophila melanogaster , 2012, Cytoskeleton.

[5]  Valerie C. Coffman,et al.  Contractile‐ring assembly in fission yeast cytokinesis: Recent advances and new perspectives , 2012, Cytoskeleton.

[6]  D. Gerlich,et al.  Molecular control of animal cell cytokinesis , 2012, Nature Cell Biology.

[7]  P. Frenette,et al.  An Anillin-Ect2 Complex Stabilizes Central Spindle Microtubules at the Cortex during Cytokinesis , 2012, PloS one.

[8]  K. B. Shannon IQGAP Family Members in Yeast, Dictyostelium, and Mammalian Cells , 2012, International journal of cell biology.

[9]  G. Hickson,et al.  Anillin Acts as a Bifunctional Linker Coordinating Midbody Ring Biogenesis during Cytokinesis , 2012, Current Biology.

[10]  F. Sicheri,et al.  Cleavage Furrow Organization Requires PIP2-Mediated Recruitment of Anillin , 2012, Current Biology.

[11]  Kuan-Chung Su,et al.  Targeting of the RhoGEF Ect2 to the equatorial membrane controls cleavage furrow formation during cytokinesis. , 2011, Developmental cell.

[12]  Junxia Wang,et al.  Proper regulation of Cdc42 activity is required for tight actin concentration at the equator during cytokinesis in adherent mammalian cells. , 2011, Experimental cell research.

[13]  M. Balasubramanian,et al.  IQGAP-Related Rng2p Organizes Cortical Nodes and Ensures Position of Cell Division in Fission Yeast , 2011, Current Biology.

[14]  K. Gould,et al.  Temporal Control of Contractile Ring Assembly by Plo1 Regulation of Myosin II Recruitment by Mid1/Anillin , 2011, Current Biology.

[15]  Valerie C. Coffman,et al.  Assembly and architecture of precursor nodes during fission yeast cytokinesis , 2011, The Journal of cell biology.

[16]  A. Maddox,et al.  The myriad roles of Anillin during cytokinesis. , 2010, Seminars in cell & developmental biology.

[17]  T. Miyake,et al.  Mitotic Down-regulation of p190RhoGAP Is Required for the Successful Completion of Cytokinesis* , 2010, The Journal of Biological Chemistry.

[18]  K. Nakano,et al.  Fission yeast IQGAP arranges actin filaments into the cytokinetic contractile ring , 2009, The EMBO journal.

[19]  R. Sonn,et al.  IQGAP1 regulates cell proliferation through a novel CDC42-mTOR pathway , 2009, Journal of Cell Science.

[20]  P. D’Avino How to scaffold the contractile ring for a safe cytokinesis - lessons from Anillin-related proteins. , 2009, Journal of cell science.

[21]  A. Kolano,et al.  Cdc42 protein acts upstream of IQGAP1 and regulates cytokinesis in mouse oocytes and embryos. , 2008, Developmental biology.

[22]  Hisashi Nojima,et al.  IQGAP3 regulates cell proliferation through the Ras/ERK signalling cascade , 2008, Nature Cell Biology.

[23]  M. Glotzer,et al.  Anillin Is a Scaffold Protein That Links RhoA, Actin, and Myosin during Cytokinesis , 2008, Current Biology.

[24]  W. Bahou,et al.  Development of Hepatocellular Carcinoma in Iqgap2-Deficient Mice Is IQGAP1 Dependent , 2008, Molecular and Cellular Biology.

[25]  J. Pringle,et al.  Identification of yeast IQGAP (Iqg1p) as an anaphase-promoting-complex substrate and its role in actomyosin-ring-independent cytokinesis. , 2007, Molecular biology of the cell.

[26]  K. Hahn,et al.  GEF-H1 modulates localized RhoA activation during cytokinesis under the control of mitotic kinases. , 2007, Developmental cell.

[27]  K. Kaibuchi,et al.  IQGAP3, a novel effector of Rac1 and Cdc42, regulates neurite outgrowth , 2007, Journal of Cell Science.

[28]  R. Adelstein,et al.  A Novel Guanine Nucleotide Exchange Factor, MYOGEF, is Required for Cytokinesis , 2006, Cell cycle.

[29]  D. Sacks,et al.  IQGAP1 in cellular signaling: bridging the GAP. , 2006, Trends in cell biology.

[30]  S. Narumiya,et al.  Rho GTPases in animal cell mitosis. , 2006, Current opinion in cell biology.

[31]  S. Yonemura,et al.  Centralspindlin regulates ECT2 and RhoA accumulation at the equatorial cortex during cytokinesis , 2006, Journal of Cell Science.

[32]  G. Fang,et al.  Anillin Is a Substrate of Anaphase-promoting Complex/Cyclosome (APC/C) That Controls Spatial Contractility of Myosin during Late Cytokinesis*[boxs] , 2005, Journal of Biological Chemistry.

[33]  G. Fang,et al.  MgcRacGAP controls the assembly of the contractile ring and the initiation of cytokinesis. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[34]  M. Glotzer,et al.  An ECT2–centralspindlin complex regulates the localization and function of RhoA , 2005, The Journal of cell biology.

[35]  F. Matsumura Regulation of myosin II during cytokinesis in higher eukaryotes. , 2005, Trends in cell biology.

[36]  K. Kaibuchi,et al.  IQGAP1: a key regulator of adhesion and migration , 2005, Journal of Cell Science.

[37]  B. Nusgens,et al.  Cdc42 downregulates MMP-1 expression by inhibiting the ERK1/2 pathway , 2005, Journal of Cell Science.

[38]  S. Narumiya,et al.  Ect2 and MgcRacGAP regulate the activation and function of Cdc42 in mitosis , 2005, The Journal of cell biology.

[39]  A. Straight,et al.  Anillin binds nonmuscle myosin II and regulates the contractile ring. , 2004, Molecular biology of the cell.

[40]  S. Narumiya,et al.  Ect 2 and MgcRacGAP regulate the activation and function of Cdc 42 in mitosis , 2005 .

[41]  J. Yates,et al.  Dissection of the Mammalian Midbody Proteome Reveals Conserved Cytokinesis Mechanisms , 2004, Science.

[42]  I. Mabuchi,et al.  An IQGAP-like protein is involved in actin assembly together with Cdc42 in the sea urchin egg. , 2003, Cell motility and the cytoskeleton.

[43]  A. Ridley,et al.  IQGAP1 Promotes Cell Motility and Invasion* , 2003, Journal of Biological Chemistry.

[44]  G. Bloom,et al.  IQGAPs: integrators of the cytoskeleton, cell adhesion machinery, and signaling networks. , 2003, Cell motility and the cytoskeleton.

[45]  Timothy J Mitchison,et al.  Dissecting Temporal and Spatial Control of Cytokinesis with a Myosin II Inhibitor , 2003, Science.

[46]  M. Glotzer,et al.  Central spindle assembly and cytokinesis require a kinesin-like protein/RhoGAP complex with microtubule bundling activity. , 2002, Developmental cell.

[47]  K. Oegema,et al.  Functional Analysis of a Human Homologue of the Drosophila Actin Binding Protein Anillin Suggests a Role in Cytokinesis , 2000, The Journal of cell biology.

[48]  R. Bronson,et al.  Gastric Hyperplasia in Mice Lacking the Putative Cdc42 Effector IQGAP1 , 2000, Molecular and Cellular Biology.

[49]  K. B. Shannon,et al.  The multiple roles of Cyk1p in the assembly and function of the actomyosin ring in budding yeast. , 1999, Molecular biology of the cell.

[50]  D. Herion,et al.  Binding of myosin essential light chain to the cytoskeleton-associated protein IQGAP1. , 1998, Biochemical and biophysical research communications.

[51]  M. Balasubramanian,et al.  Rng2p, a protein required for cytokinesis in fission yeast, is a component of the actomyosin ring and the spindle pole body , 1998, Current Biology.

[52]  J. Chant,et al.  An IQGAP-related protein controls actin-ring formation and cytokinesis in yeast , 1997, Current Biology.

[53]  S. Yokoyama,et al.  Dictyostelium IQGAP-related Protein Specifically Involved in the Completion of Cytokinesis , 1997, The Journal of cell biology.

[54]  P. Polakis,et al.  IQGAP1, a calmodulin‐binding protein with a rasGAP‐related domain, is a potential effector for cdc42Hs. , 1996, The EMBO journal.

[55]  M. Yamamoto Fission yeast. , 1989, Biotechnology.