The Arp2/3 activator WASH regulates α5β1-integrin-mediated invasive migration

J Cell Sci. 2011 Nov 15;124(Pt 22):3753-9. doi: 10.1242/jcs.080986. Epub 2011 Nov 23.

Abstract

The actin cytoskeleton provides scaffolding and physical force to effect fundamental processes such as motility, cytokinesis and vesicle trafficking. The Arp2/3 complex nucleates actin structures and contributes to endocytic vesicle invagination and trafficking away from the plasma membrane. Internalisation and directed recycling of integrins are major driving forces for invasive cell motility and potentially for cancer metastasis. Here, we describe a direct requirement for WASH and Arp2/3-mediated actin polymerisation on the endosomal membrane system for α5β1 integrin recycling. WASH regulates the trafficking of endosomal α5β1 integrin to the plasma membrane and is fundamental for integrin-driven cell morphology changes and integrin-mediated cancer cell invasion. Thus, we implicate WASH and Arp2/3-driven actin nucleation in receptor recycling leading to invasive motility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin-Related Protein 2-3 Complex / genetics
  • Actin-Related Protein 2-3 Complex / metabolism*
  • Actins / metabolism
  • Animals
  • Cell Line, Tumor
  • Cell Membrane / genetics
  • Cell Membrane / metabolism
  • Cell Movement*
  • Endosomes / genetics
  • Endosomes / metabolism
  • Humans
  • Integrin alpha5beta1 / genetics
  • Integrin alpha5beta1 / metabolism*
  • Neoplasm Invasiveness
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neoplasms / physiopathology*
  • Protein Transport
  • Wiskott-Aldrich Syndrome Protein / genetics
  • Wiskott-Aldrich Syndrome Protein / metabolism*

Substances

  • Actin-Related Protein 2-3 Complex
  • Actins
  • Integrin alpha5beta1
  • Wiskott-Aldrich Syndrome Protein