Finn D M, Ohlendieck K
Department of Pharmacology, University College Dublin, Belfield, Dublin 4, Ireland.
Biochim Biophys Acta. 1998 Mar 13;1370(2):325-36. doi: 10.1016/s0005-2736(97)00283-6.
The surface component beta-dystroglycan is a member of the dystrophin-glycoprotein complex providing a trans-sarcolemmal linkage between the actin membrane cytoskeleton and the extracellular matrix component laminin-alpha2. Although abnormalities in this complex are involved in the pathophysiology of various neuromuscular disorders, little is known about the organization of dystrophin-associated glycoproteins in diaphragm and brain. We therefore investigated the oligomerization of beta-dystroglycan and its connection with the most abundant dystrophin homologues in these two tissues. Employing detergent solubilization and alkaline extraction procedures of native membranes, it was confirmed that beta-dystroglycan behaves like an integral surface molecule as predicted by its cDNA sequence. Immunoblot analysis following chemical crosslinking of native membranes showed that beta-dystroglycan has a tendency to form high-molecular-mass complexes. Within these crosslinkable complexes, immuno-reactive overlaps were observed between beta-dystroglycan, alpha-dystroglycan, laminin and 427 kDa dystrophin in diaphragm and skeletal muscle. In synaptosomes, the major brain dystrophin isoform Dp116 also exhibited an immuno-reactive overlap with members of the dystroglycan complex. These findings demonstrate that beta-dystroglycan does not exist as a monomer in native membranes and imply that certain dystrophin isoforms and dystrophin-associated components interact with this surface protein in diaphragm and brain as has been previously shown for skeletal and heart muscle.
