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


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.

SUBMITTER: Ramesh N 

PROVIDER: S-EPMC4097659 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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

Ramesh Narayanaswamy N   Massaad Michel J MJ   Kumar Lalit L   Koduru Suresh S   Sasahara Yoji Y   Anton Ines I   Bhasin Manoj M   Libermann Towia T   Geha Raif R  

Molecular and cellular biology 20140701 14


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-re  ...[more]

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