PMID:12473693

Citation	DeMali, KA, Barlow, CA and Burridge, K (2002) Recruitment of the Arp2/3 complex to vinculin: coupling membrane protrusion to matrix adhesion. J. Cell Biol. 159:881-91
Abstract	Cell migration involves many steps, including membrane protrusion and the development of new adhesions. Here we have investigated whether there is a link between actin polymerization and integrin engagement. In response to signals that trigger membrane protrusion, the actin-related protein (Arp)2/3 complex transiently binds to vinculin, an integrin-associated protein. The interaction is regulated, requiring phosphatidylinositol-4,5-bisphosphate and Rac1 activation, and is sufficient to recruit the Arp2/3 complex to new sites of integrin aggregation. Binding of the Arp2/3 complex to vinculin is direct and does not depend on the ability of vinculin to associate with actin. We have mapped the binding site for the Arp2/3 complex to the hinge region of vinculin, and a point mutation in this region selectively blocks binding to the Arp2/3 complex. Compared with WT vinculin, expression of this mutant in vinculin-null cells results in diminished lamellipodial protrusion and spreading on fibronectin. The recruitment of the Arp2/3 complex to vinculin may be one mechanism through which actin polymerization and membrane protrusion are coupled to integrin-mediated adhesion.
Links	PubMed PMC2173392 Online version:10.1083/jcb.200206043
Keywords	3T3 Cells; Actin-Related Protein 2; Actin-Related Protein 3; Actins/metabolism; Androstadienes/pharmacology; Animals; Binding Sites/genetics; Cell Adhesion; Cell Line; Cell Movement; Cells, Cultured; Cytoskeletal Proteins/metabolism; Embryo, Mammalian; Epidermal Growth Factor/pharmacology; Extracellular Matrix/metabolism; Fibronectins/physiology; Green Fluorescent Proteins; HeLa Cells; Humans; Integrins/metabolism; Luminescent Proteins/metabolism; Mice; Phosphatidylinositol 3-Kinases/antagonists & inhibitors; Phosphatidylinositol 3-Kinases/pharmacology; Point Mutation; Protein Binding; Pseudopodia/metabolism; Recombinant Fusion Proteins/metabolism; Vinculin/antagonists & inhibitors; Vinculin/chemistry; Vinculin/genetics; Vinculin/metabolism; rac1 GTP-Binding Protein/metabolism
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