Characterization of the intermolecular associations of the dystrophin-associated glycoprotein complex in retinal Muller glial cells

The abnormal retinal neurotransmission observed in Duchenne muscular dystro phy patients has been attributed to altered expression of C-terminal produc ts of the dystrophin gene in this tissue. Muller glial cells from rat retin a express dystrophin protein Dp71, utrophin and the members of the dystroph in-associated glycoprotein complex (DGC), namely beta -dystroglycan, delta- and gamma -sarcoglycans and alpha1-syntrophin, The DGC could function in m uscle as a link between the cystoskeleton and the extracellular matrix, as well as a signaling complex. However, other than in muscle the composition and intermolecular associations among members of the DGC are still unknown. Here we demonstrate that Dp71 and/or utrophin from rat retinal Muller glia l cells form a complex: with beta -dystroglycan, delta -sarcoglycan and alp ha1-syntrophin. We also show that beta -dystroglycan is associated with alp ha -dystrobrevin-1 and PSD-93 and that anti-PSD antibodies coimmunoprecipit ated alpha1-syntrophin with PSD-93, By overlay experiments we also found th at Dp71and/or utrophin and alpha -dystroglycan from Muller cells could bind to actin and laminin, respectively. These results indicate that the DGC co uld have both structural and signaling functions in retina. On the basis of our accumulated evidence, we propose a hypothetical model for the molecula r organization of the dystrophin-associated glycoprotein complex in retinal Muller glial cells, which would be helpful for understanding its function in the central nervous system.