Dystrophin-glycoprotein complex and Ras and Rho GTPase signaling are altered in muscle atrophy

The dystrophin-glycoprotein complex (DGC)is a sarcolemmal complex whose defects cause muscular dystrophies. Thenormal function of this complex is not clear. We have proposed thatthis is a signal transduction complex, signaling normal interactionswith matrix laminin, and that the response is normal growth andhomeostasis. If so, the complex and its signaling should be altered inother physiological states such as atrophy. The amount of some of the DGC proteins, including dystrophin, -dystroglycan, and-sarcoglycan, is reduced significantly in rat skeletal muscleatrophy induced by tenotomy. Furthermore, H-Ras, RhoA, and Cdc42decrease in expression levels and activities in muscle atrophy. Whenthe small GTPases were assayed after laminin or -dystroglycandepletion, H-Ras, Rac1, and Cdc42 activities were reduced, suggesting aphysical linkage between the DGC and the GTPases. Dominant-negativeCdc42, introduced with a retroviral vector, resulted in fibers thatappeared atrophic. These data support a putative role for the DGC intransduction of mechanical signals in muscle.