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

Kinley AW, Weed SA, Weaver AM, Karginov AV, Bissonette E, Cooper JA, Parsons JT
Curr Biol. 2003 13 (5): 384-93

PMID: 12620186 · DOI:10.1016/s0960-9822(03)00107-6

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.

MeSH Terms (14)

Actin-Related Protein 2 Actin-Related Protein 3 Actins Animals Carrier Proteins Cell Membrane CHO Cells Cortactin Cricetinae Cytoskeletal Proteins Humans Intracellular Signaling Peptides and Proteins Microfilament Proteins Protein Structure, Tertiary

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