Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Kabrawala S

PROVIDER: S-EPMC7112243 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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

Kabrawala Shail S Zimmer Margaret D MD Campellone Kenneth G KG

PLoS genetics 20200320 3

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 ...[more]

PMID: 32196488

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Dataset Information

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

Publications

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

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