Mechanism and function of formins in the control of actin assembly.
Formins are a widely expressed family of proteins that govern cell shape, adhesion, cytokinesis, and morphogenesis by remodeling the actin and microtubule cytoskeletons. These large multidomain proteins associate with a variety of other cellular factors and directly nucleate actin polymerization through a novel mechanism. The signature formin homology 2 (FH2) domain initiates filament assembly and remains persistently associated with the fast-growing barbed end, enabling rapid insertion of actin subunits while protecting the end from capping proteins. On the basis of structural and mechanistic work, an integrated model is presented for FH2 processive motion. The adjacent FH1 domain recruits profilin-actin complexes and accelerates filament elongation. The most predominantly expressed formins in animals and fungi are autoinhibited through intramolecular interactions and appear to be activated by Rho GTPases and additional factors. Other classes of formins lack the autoinhibitory and/or Rho-binding domains and thus are likely to be controlled by alternative mechanisms.
Goode
Bruce L
BL
Department of Biology and Rosenstiel Basic Medical Science Research Center, Brandeis University, Waltham, Massachusetts 02454, USA. goode@brandeis.edu
Eck
Michael J
MJ
D000199:Actins / Q000737:chemistry / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D016764:Cell Polarity; D048749:Cytokinesis / Q000502:physiology; D004705:Endocytosis / Q000502:physiology; D004789:Enzyme Activation; D005326:Fetal Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism; D000080865:Formins; D006801:Humans; D008840:Microfilament Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D008958:Models, Molecular; D009024:Morphogenesis; D009687:Nuclear Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism; D051304:Profilins / Q000378:metabolism; D011487:Protein Conformation; D020033:Protein Isoforms / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D005326:Fetal Proteins; D000080865:Formins; D008840:Microfilament Proteins; D009687:Nuclear Proteins; D051304:Profilins; D020033:Protein Isoforms; D020741:rho GTP-Binding Proteins