Palladin Regulates Cell and Extracellular Matrix Interaction through Maintaining Normal Actin Cytoskeleton Architecture and Stabilizing Beta1-integrin.

摘要

Cell and extracellular matrix (ECM) interaction plays an important role in development and normal cellular function. Cell adhesion and cell spreading on ECM are two basic cellular behaviours related to cell-ECM interaction. Here we show that pelladin, a novel actin cytoskeleton-associated protein, is actively involved In the regulation of cell-ECM interaction. It was found that palladin-deficient mouse embryonic fibroblasts (MEFs) display decreased cell adhesion and compromised cell spreading on various ECMs.Disorganized actln cytoskeleton architecture characterized by faint stress fiboers, less lamellipodia and focal adhesions can account for the weakened cell-ECM interaction in palladin+ MEFs. Furthermore,decreased polymerized filament actin and increased globular actin can be observed in palladin+ MEFs,strongly suggesting that palladin is essential for the formation or stabillzation of polymerized filament actin. Elevated phospho-cofilin level and proper responses in cofilin phosphorylation to either Rho signal agonist or antagonist in palladin+ MEFs indicate that disrupted stress fibers in palladin+ MEFs is not associated with cofilin phosphorylation. More interestingly, the protein level of ECM receptor β1-Integrin is dramatically decreased in MEFs lacking pailadin. Down-regulation of β1-integrin protein can be restored by proteasome inhibitor MG-132 treatment All these data implicate that palladin is essential for cell-ECM interaction through maintaining normal actin cytoskeleton architecture and stailizing β1-integrin protein.