title: Involvement of IQGAP family proteins in the regulation of mammalian cell cytokinesis.
abstract: 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.
authors.affiliation: Department of Cell Biology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Adachi
authors.forename: Asami
authors.initials: A
authors.lastname: Kawasaki
authors.forename: Hisashi
authors.initials: H
authors.lastname: Nojima
authors.forename: Eisuke
authors.initials: E
authors.lastname: Nishida
authors.forename: Sachiko
authors.initials: S
authors.lastname: Tsukita
mesh_terms: D000705:Anaphase; D000818:Animals; D003285:Contractile Proteins / Q000378:metabolism; D048749:Cytokinesis; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells / Q000166:cytology; D006367:HeLa Cells / Q000166:cytology; D006801:Humans; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D020703:ras GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D003285:Contractile Proteins; C489850:ECT2 protein, human; D020690:GTPase-Activating Proteins; C101203:IQ motif containing GTPase activating protein 1; C101002:IQGAP2 protein, human; C000594387:IQGAP3 protein, human; D011518:Proto-Oncogene Proteins; C095886:anillin; D020703:ras GTPase-Activating Proteins; C066737:RHOA protein, human; D020742:rhoA GTP-Binding Protein