Caveolin-1 inhibits neurite growth by blocking Rac1/Cdc42 and p21-activated kinase 1 interactions

Growth factors such as basic fibroblast growth factors (bFGFs) could induce the differentiation of mouse neuroblastoma cells. We examine the effect of caveolin-1 on bFGF-induced differentiation of N2a cells. Caveolin-1 blocked the formation of neurites and the phosphorylation of Erk upon bFGF treatment in N2a cells. Active mutants of Rho family small GTPases (Rac1 and Cdc42) could not affect the inhibitory effect of caveolin-1, but we could restore the differentiation of N2a cells by introducing active mutants of p21-activated kinase 1 (PAK1). Over-expressed caveolin-1 could be coimmunoprecipitated with PAK1, which interrupted the steady-state Racl/Cdc42-PAK1 interactions. From these results, we suggest that the up-regulated caveolin-1 in neuronal cells can inhibit the bFGF signaling pathway from small GTPases to PAK1 by directly binding to PAK1.