title: Formins as effector proteins of Rho GTPases.
abstract: Formin proteins were recognized as effectors of Rho GTPases some 15 years ago. They contribute to different cellular actin cytoskeleton structures by their ability to polymerize straight actin filaments at the barbed end. While not all formins necessarily interact with Rho GTPases, a subgroup of mammalian formins, termed Diaphanous-related formins or DRFs, were shown to be activated by small GTPases of the Rho superfamily. DRFs are autoinhibited in the resting state by an N- to C-terminal interaction that renders the central actin polymerization domain inactive. Upon the interaction with a GTP-bound Rho, Rac, or Cdc42 GTPase, the C-terminal autoregulation domain is displaced from its N-terminal recognition site and the formin becomes active to polymerize actin filaments. In this review we discuss the current knowledge on the structure, activation, and function of formin-GTPase interactions for the mammalian formin families Dia, Daam, FMNL, and FHOD. We describe both direct and indirect interactions of formins with GTPases, which lead to formin activation and cytoskeletal rearrangements. The multifaceted function of formins as effector proteins of Rho GTPases thus reflects the diversity of the actin cytoskeleton in cells.
authors.affiliation: Center of Advanced European Studies and Research (caesar); Group Physical Biochemistry; Bonn, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Kühn
authors.affiliation: Center of Advanced European Studies and Research (caesar); Group Physical Biochemistry; Bonn, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Geyer
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D005326:Fetal Proteins / Q000737:chemistry / Q000378:metabolism*; D000080865:Formins; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism*; D008840:Microfilament Proteins / Q000737:chemistry / Q000378:metabolism*; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D020741:rho GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C491464:Diap1 protein, mouse; C586375:FHOD1 protein, mouse; D005326:Fetal Proteins; C413382:Fmnl1 protein, mouse; D000080865:Formins; D047908:Intracellular Signaling Peptides and Proteins; D008840:Microfilament Proteins; D009687:Nuclear Proteins; C500365:Daam1 protein, mouse; D020741:rho GTP-Binding Proteins
keywords: Cdc42; Daam1; Daam2; FHOD1; FHOD3; FMNL1; FMNL2; FMNL3; ROCK; Rac; Rho; filopodia; formin; lamellipodium; mDia1; mDia2; mDia3; stress fiber