TY - JOUR
T1 - Binding of the WASP/N-WASP-interacting protein WIP to actin regulates focal adhesion assembly and adhesion
AU - Ramesh, Narayanaswamy
AU - Massaad, Michel J.
AU - Kumar, Lalit
AU - Koduru, Suresh
AU - Sasahara, Yoji
AU - Anton, Ines
AU - Bhasin, Manoj
AU - Libermann, Towia
AU - Geha, Raif
PY - 2014/7
Y1 - 2014/7
N2 - 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.
AB - 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.
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U2 - 10.1128/MCB.00017-14
DO - 10.1128/MCB.00017-14
M3 - Article
C2 - 24797074
AN - SCOPUS:84902670180
SN - 0270-7306
VL - 34
SP - 2600
EP - 2610
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
IS - 14
ER -