Cortactin interacts with WIP in regulating Arp2/3 activation and membrane protrusion.
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.
Kinley
Andrew W
AW
Department of Microbiology, Health Sciences Center, University of Virginia, Charlottesville, VA 22908, USA.
Weed
Scott A
SA
Weaver
Alissa M
AM
Karginov
Andrei V
AV
Bissonette
Eric
E
Cooper
John A
JA
Parsons
J Thomas
JT
D051377:Actin-Related Protein 2; D051378:Actin-Related Protein 3; D000199:Actins / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D002352:Carrier Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D051356:Cortactin; D006224:Cricetinae; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008840:Microfilament Proteins / Q000378:metabolism*; D017434:Protein Structure, Tertiary
C495926:ACTR2 protein, human; C495928:ACTR3 protein, human; D051377:Actin-Related Protein 2; D051378:Actin-Related Protein 3; D000199:Actins; C495868:CTTN protein, human; D002352:Carrier Proteins; D051356:Cortactin; D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008840:Microfilament Proteins; C109903:WIPF1 protein, human