title: Dia1 and IQGAP1 interact in cell migration and phagocytic cup formation.
abstract: The Diaphanous-related formin Dia1 nucleates actin polymerization, thereby regulating cell shape and motility. Mechanisms that control the cellular location of Dia1 to spatially define actin polymerization are largely unknown. In this study, we identify the cytoskeletal scaffold protein IQGAP1 as a Dia1-binding protein that is necessary for its subcellular location. IQGAP1 interacts with Dia1 through a region within the Diaphanous inhibitory domain after the RhoA-mediated release of Dia1 autoinhibition. Both proteins colocalize at the front of migrating cells but also at the actin-rich phagocytic cup in macrophages. We show that IQGAP1 interaction with Dia1 is required for phagocytosis and phagocytic cup formation. Thus, we identify IQGAP1 as a novel component involved in the regulation of phagocytosis by mediating the localization of the actin filament nucleator Dia1.
authors.affiliation: Institute of Pharmacology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Dominique T
authors.initials: DT
authors.lastname: Brandt
authors.forename: Sabrina
authors.initials: S
authors.lastname: Marion
authors.forename: Gareth
authors.initials: G
authors.lastname: Griffiths
authors.forename: Takashi
authors.initials: T
authors.lastname: Watanabe
authors.forename: Kozo
authors.initials: K
authors.lastname: Kaibuchi
authors.forename: Robert
authors.initials: R
authors.lastname: Grosse
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018929:Cell Culture Techniques; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D004926:Escherichia coli / Q000235:genetics; D000080865:Formins; D006367:HeLa Cells; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008957:Models, Genetic; D009154:Mutation; D041681:NIH 3T3 Cells; D010587:Phagocytosis / Q000502:physiology*; D020703:ras GTPase-Activating Proteins / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C108962:DIAPH1 protein, human; C491464:Diap1 protein, mouse; D000080865:Formins; C101203:IQ motif containing GTPase activating protein 1; D020703:ras GTPase-Activating Proteins