Cortactin interacts with WIP in regulating Arp2/3 activation and membrane protrusion

Andrew W. Kinley, Scott A. Weed, Alissa M. Weaver, Andrei V. Karginov, Eric Bissonette, John A. Cooper, J. Thomas Parsons

Research output: Contribution to journalArticlepeer-review

145 Scopus citations

Abstract

Background: Modulation of actin cytoskeleton assembly is an integral step in many cellular events. A key regulator of actin polymerization is Arp2/3 complex. Cortactin, an F-actin binding protein that localizes to membrane ruffles, is an activator of Arp2/3 complex. Results: A yeast two-hybrid screen revealed the interaction of the cortactin Src homology 3 (SH3) domain with a peptide fragment derived from a cDNA encoding a region of WASp-Interacting Protein (WIP). GST-cortactin interacted with WIP in an SH3-dependent manner. The subcellular localization of cortactin and WIP coincided at the cell periphery. WIP increased the efficiency of cortactin-mediated Arp2/3 complex activation of actin polymerization in a concentration-dependent manner. Lastly, coexpression of cortactin and WIP stimulated membrane protrusions. Conclusions: WIP, a protein involved in filopodia formation, binds to both actin monomers and cortactin. Thus, recruitment of actin monomers to a cortactin-activated Arp2/3 complex likely leads to the observed increase in cortactin activation of Arp2/3 complex by WIP. These data suggest that a cortactin-WIP complex functions in regulating actin-based structures at the cell periphery.

Original languageEnglish
Pages (from-to)384-393
Number of pages10
JournalCurrent Biology
Volume13
Issue number5
DOIs
StatePublished - Mar 4 2003

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