Regulatory roles of fibronectin and integrin 5 in reorganization of the actin cytoskeleton and completion of adipogenesis

Cellular differentiation is characterized by changes in cell morphology that are largely determined by actin dynamics. We previously showed that depolymerization of the actin cytoskeleton triggers the differentiation of preadipocytes into mature adipocytes as a result of inhibition of the transcriptional coactivator activity of megakaryoblastic leukemia 1 (MKL1). The extracellular matrix (ECM) influences cell morphology via interaction with integrins, and reorganization of the ECM is associated with cell differentiation. Here we show that interaction between actin dynamics and ECM rearrangement plays a key role in adipocyte differentiation. We found that depolymerization of the actin cytoskeleton precedes disruption and degradation of fibrillar fibronectin (FN) structures at the cell surface after the induction of adipogenesis in cultured preadipocytes. A FN matrix suppressed both reorganization of the actin cytoskeleton into the pattern characteristic of adipocytes and terminal adipocyte differentiation, and these inhibitory effects were overcome by knockdown of integrin alpha 5 (ITG alpha 5). Peroxisome proliferator-activated receptor gamma was required for down-regulation of FN during adipocyte differentiation, and MKL1 was necessary for the expression of ITG alpha 5. Our findings suggest that cell-autonomous down-regulation of FN-ITG alpha 5 interaction contributes to reorganization of the actin cytoskeleton and completion of adipocyte differentiation.