Recruitment of Dbl by ezrin and dystroglycan drives membrane proximal Cdc42 activation and filopodia formation

Clare L. Batchelor, Jen R. Higginson, Yun Ju Chen, Cristina Vanni, Alessandra Eva, Steve J. Winder

Research output: Contribution to journalArticle

Abstract

Dystroglycan is an essential laminin binding cell adhesion molecule, which is also an adaptor for several SH2 domain-containing signaling molecules and as a scaffold for the ERK-MAP kinase cascade. Loss of dystroglycan function is implicated in muscular dystrophies and the aetiology of epithelial cancers. We have previously demonstrated a role for dystroglycan and ezrin in the formation of filopodia structures. Here we demonstrate the existence of a dystroglycan:ezrin:Dbl complex that is targeted to the membrane by dystroglycan where it drives local Cdc42 activation and the formation of filopodia. Deletion of an ezrin binding site in dystroglycan prevented the association with ezrin and Dbl and the formation of filopodia. Furthermore, expression of the dystroglycan cytoplasmic domain alone had a dominant-negative effect on filopodia formation and Cdc42 activation by sequestering ezrin and Dbl away from the membrane. Depletion of dystroglycan inhibited Cdc42-induced filopodia formation. For the first time we also demonstrate co-localization of Cdc42 and dystroglycan at the tips of dynamic filopodia.

Original languageEnglish
Pages (from-to)353-363
Number of pages11
JournalCell Cycle
Volume6
Issue number3
Publication statusPublished - Feb 1 2007

Keywords

  • Actin dynamics
  • Cell motility
  • Dbl
  • Dystroglycan
  • ERM proteins
  • Rho GTPases

ASJC Scopus subject areas

  • Cell Biology
  • Biochemistry
  • Molecular Biology

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    Batchelor, C. L., Higginson, J. R., Chen, Y. J., Vanni, C., Eva, A., & Winder, S. J. (2007). Recruitment of Dbl by ezrin and dystroglycan drives membrane proximal Cdc42 activation and filopodia formation. Cell Cycle, 6(3), 353-363.