WHIMP links the actin nucleation machinery to Src-family kinase signaling during protrusion and motility

Autoři: Shail Kabrawala aff001;  Margaret D. Zimmer aff001;  Kenneth G. Campellone aff001
Působiště autorů: Department of Molecular and Cell Biology, Institute for Systems Genomics, University of Connecticut, Storrs, Connecticut, United States of America aff001
Vyšlo v časopise: WHIMP links the actin nucleation machinery to Src-family kinase signaling during protrusion and motility. PLoS Genet 16(3): e32767. doi:10.1371/journal.pgen.1008694
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1008694


Cell motility is governed by cooperation between the Arp2/3 complex and nucleation-promoting factors from the Wiskott-Aldrich Syndrome Protein (WASP) family, which together assemble actin filament networks to drive membrane protrusion. Here we identify WHIMP (WAVE Homology In Membrane Protrusions) as a new member of the WASP family. The Whimp gene is encoded on the X chromosome of a subset of mammals, including mice. Murine WHIMP promotes Arp2/3-dependent actin assembly, but is less potent than other nucleation factors. Nevertheless, WHIMP-mediated Arp2/3 activation enhances both plasma membrane ruffling and wound healing migration, whereas WHIMP depletion impairs protrusion and slows motility. WHIMP expression also increases Src-family kinase activity, and WHIMP-induced ruffles contain the additional nucleation-promoting factors WAVE1, WAVE2, and N-WASP, but not JMY or WASH. Perturbing the function of Src-family kinases, WAVE proteins, or Arp2/3 complex inhibits WHIMP-driven ruffling. These results suggest that WHIMP-associated actin assembly plays a direct role in membrane protrusion, but also results in feedback control of tyrosine kinase signaling to modulate the activation of multiple WASP-family members.

Klíčová slova:

Actin polymerization – Actins – Cell membranes – Cell motility – Cell staining – DAPI staining – Nucleation – Small interfering RNAs


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