Integrin-?5 and zyxin mediate formation of ventral stress fibers in response to transforming growth factor ?.

ABSTRACT: Cell adhesion to the extracellular matrix is an essential element of various biological processes. TGF-? cytokines regulate the matrix components and cell-matrix adhesions. The present study investigates the molecular organization of TGF-?-induced matrix adhesions. The study demonstrates that in various mouse and human epithelial cells TGF-? induces cellular structures containing 2 matrix adhesions bridged by a stretch of actin fibers. These structures are similar to ventral stress fibers (VSFs). Suppression of integrin-?5 by RNA interference reduces VSFs in majority of cells (> 75%), while overexpression of integrin-?5 fragments revealed a critical role of a distinct sequence in the cytoplasmic domain of integrin-?5 in the VSF structures. In addition, the integrity of actin fibers and Src kinase activity contribute to integrin-?5-mediated signaling and VSF formation. TGF-?-Smad signaling upregulates actin-regulatory proteins, such as caldesmon, zyxin, and zyxin-binding protein Csrp1 in mouse and human epithelial cells. Suppression of zyxin markedly inhibits formation of VSFs in response to TGF-? and integrin-?5. Zyxin is localized at actin fibers and matrix adhesions of VSFs and might bridge integrin-?5-mediated adhesions to actin fibers. These findings provide a platform for defining the molecular mechanism regulating the organization and activities of VSFs in response to TGF-?.

SUBMITTER: Bianchi-Smiraglia A 

PROVIDER: S-EPMC3895427 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature