Binding of the WASP/N-WASP-interacting protein WIP to actin regulates focal adhesion assembly and adhesion

Narayanaswamy Ramesh, Michel J. Massaad, Lalit Kumar, Suresh Koduru, Yoji Sasahara, Ines Anton, Manoj Bhasin, Towia Libermann, Raif Geha

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The actin cytoskeleton is essential for cell adhesion and migration, functions important for tumor invasion. In addition to binding N-WASP/WASP, WIP binds and stabilizes F-actin. WIP-/- fibroblasts were used to test the role of WIP in F-actin function. WIP-/- cells had defective focal adhesion (FA), stress fiber assembly, and adherence to substrates, functions that were restored by transduction of wild-type WIP. Protein and mRNA levels of several FA constituents regulated by the myocardin-related transcription factor (MRTF)-serum response factor (SRF) transcription factor complex were reduced in WIP-/- fibroblasts. The level of G-actin, which sequesters MRTF in the cytoplasm, was increased, and nuclear localization of MRTF-A and SRF was reduced, in WIP-/- fibroblasts. Transfection of an MRTF-A mutant that constitutively translocates to the nucleus or transfection of constitutively active SRF restored FA and stress fiber assembly. Fibroblasts from knock-in mice expressing a WIP mutant that fails to bind actin phenocopied WIP-/- fibroblasts. Thus, WIP is a novel regulator of FA assembly and cell adhesion.

Original languageEnglish
Pages (from-to)2600-2610
Number of pages11
JournalMolecular and cellular biology
Volume34
Issue number14
DOIs
Publication statusPublished - 2014 Jul

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Ramesh, N., Massaad, M. J., Kumar, L., Koduru, S., Sasahara, Y., Anton, I., Bhasin, M., Libermann, T., & Geha, R. (2014). Binding of the WASP/N-WASP-interacting protein WIP to actin regulates focal adhesion assembly and adhesion. Molecular and cellular biology, 34(14), 2600-2610. https://doi.org/10.1128/MCB.00017-14