Disatnik et al. report studies dissecting the role of the protein kinase C (PKC) substrate MARCKS (myristoylated alanine-rich C-kinase substrate) in integrin-induced cell spreading. Their results indicate that MARCKS has two sequential roles: one to promote attachment of the cells to the substrate, and the other to promote cell spreading associated with polymerization and cross-linking of actin. The two phases appear to result from distinct localizations of the MARCKS protein. Within 30 min of plating of mouse myoblasts on fibronectin-coated dishes, α5ß1 integrin-mediated signals cause activation of PKC; dissociation of MARCKS, which is initially associated with the plasma membrane; and movement to the cytosol. When this process was blocked in cells ectopically expressing a MARCKS mutant lacking PKC phosphorylation sites, there was a nearly complete loss of attachment and spreading of cells. At later time points, MARCKS becomes dephosphorylated and returns to the plasma membrane, a process that requires an N-terminal myristoylation domain. Expression of MARCKS in which the myristoylation site was mutated yielded cells that underwent initial attachment but failed to spread. MARCKS is known to directly and indirectly influence actin cross-linking. Thus, the authors propose that the bidirectional translocation of MARCKS provides a key link between integrin signaling and control of cytoskeletal dynamics.
M. H. Disatnik, S. C. Boutet, W. Pacio, A. Y. Chan, L. B. Ross, C. H. Lee, T. A. Rando, The bi-directional translocation of MARCKS between membrane and cytosol regulates integrin-mediated muscle cell spreading. J. Cell Sci. 117, 4469-4479 (2004). [Abstract] [Full Text]