GRASP and IPCEF promote ARF-to-Rac signaling and cell migration by coordinating the association of ARNO/cytohesin 2 with Dock180.
ARFs are small GTPases that regulate vesicular trafficking, cell shape, and movement. ARFs are subject to extensive regulation by a large number of accessory proteins. The many different accessory proteins are likely specialized to regulate ARF signaling during particular processes. ARNO/cytohesin 2 is an ARF-activating protein that promotes cell migration ... and cell shape changes. We report here that protein-protein interactions mediated by the coiled-coil domain of ARNO are required for ARNO induced motility. ARNO lacking the coiled-coil domain does not promote migration and does not induce ARF-dependent Rac activation. We find that the coiled-coil domain promotes the assembly of a multiprotein complex containing both ARNO and the Rac-activating protein Dock180. Knockdown of either GRASP/Tamalin or IPCEF, two proteins known to bind to the coiled-coil of ARNO, prevents the association of ARNO and Dock180 and prevents ARNO-induced Rac activation. These data suggest that scaffold proteins can regulate ARF dependent processes by biasing ARF signaling toward particular outputs.
Mesh Terms:
ADP-Ribosylation Factors, Animals, Carrier Proteins, Cell Adhesion Molecules, Cell Line, Cell Movement, Dogs, Enzyme Activation, GTPase-Activating Proteins, Gene Knockdown Techniques, Humans, Membrane Proteins, Multiprotein Complexes, Protein Structure, Secondary, RNA, Small Interfering, Signal Transduction, rac GTP-Binding Proteins
ADP-Ribosylation Factors, Animals, Carrier Proteins, Cell Adhesion Molecules, Cell Line, Cell Movement, Dogs, Enzyme Activation, GTPase-Activating Proteins, Gene Knockdown Techniques, Humans, Membrane Proteins, Multiprotein Complexes, Protein Structure, Secondary, RNA, Small Interfering, Signal Transduction, rac GTP-Binding Proteins
Mol. Biol. Cell
Date: Feb. 15, 2010
PubMed ID: 20016009
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