title: Regulatory models of RhoA suppression by dematin, a cytoskeletal adaptor protein.
abstract: Cell motility, adhesion and actin cytoskeletal rearrangements occur upon integrin-engagement to the extracellular matrix and activation of the small family of Rho GTPases, RhoA, Rac1 and Cdc42. The activity of the GTPases is regulated through associations with guanine nucleotide exchange factors (GEFs), GTPase activating proteins (GAPs) and guanine dissociation inhibitors (GDIs). Recent studies have demonstrated a critical role for actin-binding proteins, such as ezrin, radixin and moesin (ERM), in modulating the activity of small GTPases through their direct associations with GEFs, GAPs and GDI's. Dematin, an actin binding and bundling phospho-protein was first identified and characterized from the erythrocyte membrane, and has recently been implicated in regulating cell motility, adhesion and morphology by suppressing RhoA activation in mouse embryonic fibroblasts. Although the precise mechanism of RhoA suppression by dematin is unclear, several plausible and hypothetical models can be invoked. Dematin may bind and inhibit GEF activity, form an inactive complex with GDI-RhoA-GDP, or enhance GAP function. Dematin is the first actin-binding protein identified from the erythrocyte membrane that participates in GTPase signaling, and its broad expression suggests a conserved function in multiple tissues.
authors.affiliation: Department of Pharmacology, University of Illinois College of Medicine, Chicago, USA. mmohs2@uic.edu
authors.forename: Morvarid
authors.initials: M
authors.lastname: Mohseni
authors.forename: Athar H
authors.initials: AH
authors.lastname: Chishti
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000502:physiology*; D006801:Humans; D008840:Microfilament Proteins; D010750:Phosphoproteins / Q000502:physiology*; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors* / Q000502:physiology
chemical_list: D001798:Blood Proteins; C044805:DMTN protein, human; D008840:Microfilament Proteins; D010750:Phosphoproteins; D020742:rhoA GTP-Binding Protein