%0 Journal Article
%T WHIMP links the actin nucleation machinery to Src-family kinase signaling during protrusion and motility
%A Kenneth G. Campellone
%A Margaret D. Zimmer
%A Shail Kabrawala
%J -
%D 2020
%R 10.1371/journal.pgen.1008694
%X 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
%K Cell staining
%K Small interfering RNAs
%K Actins
%K Cell membranes
%K Cell motility
%K DAPI staining
%K Actin polymerization
%K Nucleation
%U https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1008694