Abstract
Polymerization of actin in cellular membrane ruffles is triggered by the Arp2/3 complex, which in turn is activated by WAVE, a protein related to neural Wiskott-Aldrich syndrome protein (N-WASP). Although WAVE is regulated by the small guanosine triphosphate-binding protein Rac, their interaction is not direct. Miki et al. now report that IRSp53, a substrate for the insulin receptor, physically links to Rac and WAVE, and that this trimolecular complex is essential for Rac-induced membrane ruffling. Biochemical analysis identified sites of protein-protein interaction within the complex and also indicated that IRSp53-WAVE could stimulate Arp2/3-mediated actin polymerization in vitro. Hence, IRSp53, whose function is not known, may serve to recruit WAVE to Rac. Miki, H., Yamaguchi, H., Suetsugu, S., and Takenawa, T. (2000) IRSp53 is an essential intermediate between Rac and WAVE in the regulation of membrane ruffling. Nature 408 : 732-735. [Online Journal]
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