A neural Wiskott-Aldrich syndrome protein-mediated pathway for localized activation of actin polymerization that is regulated by cortactin

Stephan J. Kempiak, Hideki Yamaguchi, Corina Sarmiento, Mazen Sidani, Mousumi Ghosh, Robert J. Eddy, Vera M. Desmarais, Michael Way, John S. Condeelis, Jeffrey E. Segall

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Abstract

Activation of the epidermal growth factor (EGF) receptor can stimulate actin polymerization via the Arp2/3 complex using a number of signaling pathways, and specific stimulation conditions may control which pathways are activated. We have previously shown that localized stimulation of EGF receptor with EGF bound to beads results in localized actin polymerization and protrusion. Here we show that the actin polymerization is dependent upon activation of the Arp2/3 complex by neural Wiskott-Aldrich Syndrome protein (N-WASP) via Grb2 and Nck2. Suppression of Grb2 or Nck2 results in loss of localization of N-WASP at the activation site and reduced actin polymerization. Although cortactin has been found to synergize with N-WASP for Arp2/3-dependent actin polymerization in vitro, we find that cortactin can restrict N-WASP localization around EGF-bead-incluced protrusions. In addition, cortactin-deficient cells have increased lamellipod dynamics but show reduced net translocation, suggesting that cortactin can contribute to cell polarity by controlling the extent of Arp2/3 activation by WASP family members and the stability of the F-actin network.

Original languageEnglish (US)
Pages (from-to)5836-5842
Number of pages7
JournalJournal of Biological Chemistry
Volume280
Issue number7
DOIs
StatePublished - Feb 18 2005

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Wiskott-Aldrich Syndrome Protein
Cortactin
Polymerization
Actins
Chemical activation
Actin-Related Protein 2-3 Complex
Epidermal Growth Factor Receptor
Epidermal Growth Factor
Cell Polarity

ASJC Scopus subject areas

  • Biochemistry

Cite this

A neural Wiskott-Aldrich syndrome protein-mediated pathway for localized activation of actin polymerization that is regulated by cortactin. / Kempiak, Stephan J.; Yamaguchi, Hideki; Sarmiento, Corina; Sidani, Mazen; Ghosh, Mousumi; Eddy, Robert J.; Desmarais, Vera M.; Way, Michael; Condeelis, John S.; Segall, Jeffrey E.

In: Journal of Biological Chemistry, Vol. 280, No. 7, 18.02.2005, p. 5836-5842.

Research output: Contribution to journalArticle

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AU - Yamaguchi, Hideki

AU - Sarmiento, Corina

AU - Sidani, Mazen

AU - Ghosh, Mousumi

AU - Eddy, Robert J.

AU - Desmarais, Vera M.

AU - Way, Michael

AU - Condeelis, John S.

AU - Segall, Jeffrey E.

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