Ramesh N, Massaad MJ, Kumar L, Suresh K, Sasahara Y, Anton I, Bhasin M, Libermann T, Geha R.
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 that were restored by transduction of wild-type WIP. Protein and mRNA levels of several FA constituents regulated by the MRTF-SRF transcription factor complex were reduced in WIP−/− fibroblasts. 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 of constitutively active SRF, restored FA and stress fiber assembly. Fibroblasts from knock-in mice that express a WIP mutant that fails to bind actin phenocopied WIP−/− fibroblasts. Thus, WIP is a novel regulator of FA assembly and cell adhesion.