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

Zech, Tobias; Calaminus, Simon; Caswell, Patrick; Spence, Heather J.; Carnell, Michael; Insall, Robert H.; Norman, Jim; Machesky, Laura M.

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.

Citation

Zech, T., Calaminus, S., Caswell, P., Spence, H. J., Carnell, M., Insall, R. H., Norman, J., & Machesky, L. M. (2012). The Arp2/3 activator WASH regulates α5β1-integrin-mediated invasive migration. Journal of cell science, 124(22), 3753-3759. https://doi.org/10.1242/jcs.080986

• Journal Article Type: Article
• Acceptance Date: Nov 23, 2012
• Online Publication Date: Nov 23, 2011
• Publication Date: Nov 23, 2012
• Print ISSN: 0021-9533
• Publisher: The Company of Biologists
• Peer Reviewed: Peer Reviewed
• Volume: 124
• Issue: 22
• Pages: 3753-3759
• DOI: https://doi.org/10.1242/jcs.080986
• Keywords: Arp2/3 complex, invasion, actin assembly, integrin recycling, membrane trafficking
• Public URL: https://hull-repository.worktribe.com/output/428946