The cytoskeletal network controls c-Jun expression and glucocorticoid receptor transcriptional activity in an antagonistic and cell-type-specific manner

The physical and functional link between adhesion molecules and the cytoske letal network suggests that the cytoskeleton might mediate the transduction of cell-to-cell contact signals, which often regulate growth and different iation in an antagonistic manner. Depolymerization of the cytoskeleton in c onfluent cell cultures is reportedly sufficient to initiate DNA synthesis, Here we show that depolymerization of the cytoskeleton is also sufficient t o repress differentiation-specific gene expression. Glutamine synthetase is a glia-specific differentiation marker gene whose expression in the retina l tissue is regulated by glucocorticoids and is ultimately dependent on gli a-neuron cell contacts. Depolymerization of the actin or microtubule networ k in cells of the intact retina mimics the effects of cell separation, repr essing glutamine synthetase induction by a mechanism that involves inductio n of c-Jun and inhibition of glucocorticoid receptor transcriptional activi ty. Depolymerization of the cytoskeleton activates JNK and p38 mitogen-acti vated protein kinase and induces c-Jun expression by a signaling pathway th at depends on tyrosine kinase activity. Induction of c-Jun expression is re stricted to Muller glial cells, the only cells in the tissue that express g lutamine synthetase and maintain the ability to proliferate upon cell separ ation. Our results suggest that the cytoskeletal network might play a part in the transduction of cell contact signals to the nucleus.