title: 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.
authors.forename: Narayanaswamy
authors.initials: N
authors.lastname: Ramesh
authors.forename: Michel J
authors.initials: MJ
authors.lastname: Massaad
authors.forename: Lalit
authors.initials: L
authors.lastname: Kumar
authors.forename: Suresh
authors.initials: S
authors.lastname: Koduru
authors.forename: Yoji
authors.initials: Y
authors.lastname: Sasahara
authors.forename: Ines
authors.initials: I
authors.lastname: Anton
authors.forename: Manoj
authors.initials: M
authors.lastname: Bhasin
authors.forename: Towia
authors.initials: T
authors.lastname: Libermann
authors.forename: Raif
authors.initials: R
authors.lastname: Geha
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D003598:Cytoskeletal Proteins; D005347:Fibroblasts / Q000378:metabolism; D022001:Focal Adhesions / Q000235:genetics / Q000378:metabolism*; D055879:Gene Knock-In Techniques; D008168:Lung / Q000166:cytology; D051379:Mice; D026362:Serum Response Factor / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D026362:Serum Response Factor; D014157:Transcription Factors; C491671:Waspip protein, mouse