title: Cell division requires a direct link between microtubule-bound RacGAP and Anillin in the contractile ring.
abstract: The mitotic microtubule array plays two primary roles in cell division. It acts as a scaffold for the congression and separation of chromosomes, and it specifies and maintains the contractile-ring position. The current model for initiation of Drosophila and mammalian cytokinesis [1-5] postulates that equatorial localization of a RhoGEF (Pbl/Ect2) by a microtubule-associated motor protein complex creates a band of activated RhoA [6], which subsequently recruits contractile-ring components such as actin, myosin, and Anillin [1-3]. Equatorial microtubules are essential for continued constriction, but how they interact with the contractile apparatus is unknown. Here, we report the first direct molecular link between the microtubule spindle and the actomyosin contractile ring. We find that the spindle-associated component, RacGAP50C, which specifies the site of cleavage [1-5], interacts directly with Anillin, an actin and myosin binding protein found in the contractile ring [7-10]. Both proteins depend on this interaction for their localization. In the absence of Anillin, the spindle-associated RacGAP loses its association with the equatorial cortex, and cytokinesis fails. These results account for the long-observed dependence of cytokinesis on the continual presence of microtubules at the cortex.
authors.affiliation: Centre for the Molecular Genetics of Development, University of Adelaide, Adelaide, SA 5005, Australia.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Gregory
authors.forename: Saman
authors.initials: S
authors.lastname: Ebrahimi
authors.forename: Joanne
authors.initials: J
authors.lastname: Milverton
authors.forename: Whitney M
authors.initials: WM
authors.lastname: Jones
authors.forename: Amy
authors.initials: A
authors.lastname: Bejsovec
authors.forename: Robert
authors.initials: R
authors.lastname: Saint
mesh_terms: D000205:Actomyosin / Q000378:metabolism; D000818:Animals; D002455:Cell Division / Q000502:physiology*; D003285:Contractile Proteins / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D004330:Drosophila / Q000166:cytology* / Q000378:metabolism; D029721:Drosophila Proteins / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D031541:Fluorescence Resonance Energy Transfer; D020690:GTPase-Activating Proteins / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D008870:Microtubules / Q000378:metabolism*; D025941:Protein Interaction Mapping; D008941:Spindle Apparatus / Q000378:metabolism
chemical_list: D003285:Contractile Proteins; D029721:Drosophila Proteins; D020690:GTPase-Activating Proteins; C095886:anillin; C502951:tum protein, Drosophila; D000205:Actomyosin