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

Curr Biol. 2003 Mar 4;13(5):384-93. doi: 10.1016/s0960-9822(03)00107-6.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

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

Substances

  • ACTR2 protein, human
  • ACTR3 protein, human
  • Actin-Related Protein 2
  • Actin-Related Protein 3
  • Actins
  • CTTN protein, human
  • Carrier Proteins
  • Cortactin
  • Cytoskeletal Proteins
  • Intracellular Signaling Peptides and Proteins
  • Microfilament Proteins
  • WIPF1 protein, human