This suggests that p130Cas and Fyn interact at the plasma Ruxolitinib membrane and is in agreement with previous findings in which tyrosine phosphorylated p130Cas was shown to be associated with cell membranes in 3Y1 fibroblasts, while unphosphorylated p130Cas is located in the cytoplasm. Furthermore, the Src binding domain was shown to be essential for p130Cas membrane localization. The co-localization appears most prominent in the distal tips of cell processes where tyrosine phosphorylation of p130Cas by Fyn is likely to take place, alluding to a function in focal adhesions and process dynamics. The adapter molecule p130Cas links extracellular signals with cytoskeletal changes involving the action of integrins and Src family kinases and in lymphocytes and fibroblasts p130Cas is specifically targeted by Fyn. In oligodendrocytes, the roles of integrins and Fyn kinase in cellular differentiation and myelination have been demonstrated in several studies. Both a6b1 integrin and Fyn are involved in the outgrowth of oligodendroglial processes and myelination. Moreover, p130Cas action on actin cytoskeleton rearrangements was proposed to involve regulation of Rho-family small GTPases and these have also been implicated in oligodendroglial process formation downstream of integrin to Fyn signaling. Compatible with these findings, our data demonstrate a role of oligodendroglial p130Cas in process formation as knockdown of this protein significantly decreases the ability of cells to form lamellipodia and lamella during cell spreading and initial process outgrowth. Furthermore, reduction of p130Cas protein levels appears to affect the lateral growth of processes resulting in significantly thinner processes. Interestingly, lateral growth of oligodendrocyte processes seems to occur during active myelination as has been demonstrated recently in an in vivo myelination study in zebrafish. p130Cas has been described to mediate process formation in other cell types including neurons involving the action of Src-family kinases and we propose that this occurs in oligodendrocytes in a similar way. In correlation with the observed morphological changes, reduction of p130Cas also impedes OPC migration. It was shown recently that directional migration of OPCs depends on the action of Rho-family small GTPases activated by the cell surface protein NG2. As these GTPases have also been suggested as downstream effectors of p130Cas, it is thus likely that it contributes to the above described regulation of OPC migration. In our study, we did not address directly if a Fyn-p130Cas interaction controls migration. However, inhibition of Fyn impedes PDGF-dependent migration in OPCs and it was recently proposed that Slit2 binding to roundabout receptors inhibits OPC migration by Fyn inactivation and decreased Fyn/Robo interaction. Moreover, the Src-binding domain and the Src kinase phosphorylation sites in the substrate domain.