title: p140mDia, a mammalian homolog of Drosophila diaphanous, is a target protein for Rho small GTPase and is a ligand for profilin.
abstract: Rho small GTPase regulates cell morphology, adhesion and cytokinesis through the actin cytoskeleton. We have identified a protein, p140mDia, as a downstream effector of Rho. It is a mammalian homolog of Drosophila diaphanous, a protein required for cytokinesis, and belongs to a family of formin-related proteins containing repetitive polyproline stretches. p140mDia binds selectively to the GTP-bound form of Rho and also binds to profilin. p140mDia, profilin and RhoA are co-localized in the spreading lamellae of cultured fibroblasts. They are also co-localized in membrane ruffles of phorbol ester-stimulated sMDCK2 cells, which extend these structures in a Rho-dependent manner. The three proteins are recruited around phagocytic cups induced by fibronectin-coated beads. Their recruitment is not induced after Rho is inactivated by microinjection of botulinum C3 exoenzyme. Overexpression of p140mDia in COS-7 cells induced homogeneous actin filament formation. These results suggest that Rho regulates actin polymerization by targeting profilin via p140mDia beneath the specific plasma membranes.
authors.affiliation: Department of Pharmacology, Kyoto University Faculty of Medicine, Sakyo, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Watanabe
authors.forename: P
authors.initials: P
authors.lastname: Madaule
authors.forename: T
authors.initials: T
authors.lastname: Reid
authors.forename: T
authors.initials: T
authors.lastname: Ishizaki
authors.forename: G
authors.initials: G
authors.lastname: Watanabe
authors.forename: A
authors.initials: A
authors.lastname: Kakizuka
authors.forename: Y
authors.initials: Y
authors.lastname: Saito
authors.forename: K
authors.initials: K
authors.lastname: Nakao
authors.forename: B M
authors.initials: BM
authors.lastname: Jockusch
authors.forename: S
authors.initials: S
authors.lastname: Narumiya
mesh_terms: D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D002462:Cell Membrane / Q000378:metabolism*; D002465:Cell Movement; D003285:Contractile Proteins; D004330:Drosophila / Q000235:genetics; D029721:Drosophila Proteins; D005455:Fluorescent Antibody Technique; D000080865:Formins; D005656:Fungal Proteins / Q000235:genetics; D019204:GTP-Binding Proteins / Q000378:metabolism*; D019476:Insect Proteins / Q000235:genetics; D008024:Ligands; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D051304:Profilins; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D020742:rhoA GTP-Binding Protein
chemical_list: C105191:Bni1 protein, S cerevisiae; D002352:Carrier Proteins; D003285:Contractile Proteins; C491464:Diap1 protein, mouse; D029721:Drosophila Proteins; D000080865:Formins; D005656:Fungal Proteins; D019476:Insect Proteins; D008024:Ligands; D008840:Microfilament Proteins; C495739:Pfn1 protein, mouse; D051304:Profilins; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; C106890:diaphanous protein, Drosophila; D019204:GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein