Binding of the WASP/N-WASP-Interacting Protein WIP to Actin Regulates Focal Adhesion Assembly and Adhesion
| Autor: | Raif S. Geha, Manoj Bhasin, Suresh Koduru, Michel J. Massaad, Lalit Kumar, Inés M. Antón, Narayanaswamy Ramesh, Towia A. Libermann, Yoji Sasahara |
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| Rok vydání: | 2014 |
| Předmět: |
Serum Response Factor
Transcription factor complex Focal adhesion assembly macromolecular substances Biology Stress fiber assembly Focal adhesion Mice Serum response factor Cell Adhesion Animals Gene Knock-In Techniques Cell adhesion Lung Molecular Biology Transcription factor Focal Adhesions Binding Sites Articles Cell Biology Fibroblasts Actin cytoskeleton Cell biology Actin Cytoskeleton Cytoskeletal Proteins Carrier Proteins Transcription Factors |
| Zdroj: | Molecular and Cellular Biology. 34:2600-2610 |
| ISSN: | 1098-5549 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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