title: ADP ribosylation factor 6 (Arf6) acts through FilGAP protein to down-regulate Rac protein and regulates plasma membrane blebbing.
abstract: The small GTP-binding protein Arf6 reorganizes the actin cytoskeleton through the regulation of Rac activity. We identified FilGAP, a Rac-specific Rho GTPase-activating protein that is recruited to plasma membranes by binding to activated Arf6. FilGAP binds to Arf6 through its pleckstrin homology domain. Activated Arf6 stimulated RacGAP activity of FilGAP, and knockdown of endogenous Arf6 by siRNA suppresses FilGAP-mediated bleb formation. Mutant FilGAP lacking phosphatidylinositol 3,4,5-trisphosphate (PIP3) binding (FilGAP R39C) binds to activated Arf6 and induces bleb formation. Moreover, bleb formation induced by wild-type FilGAP occurs in the presence of phosphatidylinositol 3-kinase inhibitors, suggesting a PIP3-independent interaction between FilGAP and Arf6. We propose that FilGAP may function as a mediator of the regulation of Rac by Arf6.
authors: From the Division of Cell Biology, Department of Biosciences, School of Science, Kitasato University, 1-15-1 Kitasato, Sagamihara, Minami-ku, Kanagawa 252-0373, Japan.
authors: Kaori
authors: K
authors: Kawaguchi
authors: Koji
authors: K
authors: Saito
authors: Hisayo
authors: H
authors: Asami
authors: Yasutaka
authors: Y
authors: Ohta
mesh_terms: D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology*; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D018129:Phosphatidylinositol Phosphates / Q000235:genetics / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D000089982:ADP-Ribosylation Factor 6; C497033:ARHGAP24 protein, human; D020690:GTPase-Activating Proteins; D018129:Phosphatidylinositol Phosphates; C107953:RAC1 protein, human; C060974:phosphatidylinositol 3,4,5-triphosphate; D020727:ADP-Ribosylation Factors; C000715348:ARF6 protein, human; D020830:rac1 GTP-Binding Protein
keywords: Actin; Arf6; Cell Migration; Cell Polarization; Cytoskeleton; PI 3-kinase; Rac; Rho; Signal Transduction; Small GTPases