LOCALIZATION OF THE DYSTROPHIN BINDING-SITE AT THE CARBOXYL-TERMINUS OF BETA-DYSTROGLYCAN

Alpha- and beta-dystroglycan form a heteromeric transmembrane complex linking the extracellular matrix to the cytoskeleton. In muscle beta-d ystroglycan interacts with dystrophin on the inside of the cell and wi th alpha-dystroglycan, which binds the extracellular matrix protein la minin, on the outside. Dystroglycan is expressed not only in muscle bu t also in other tissues. We cloned beta-dystroglycan from rabbit brain by RT-PCR and expressed deletion mutants of the beta-dystroglycan cyt oplasmic domain as GST-fusion proteins. We identified the dystrophin b inding region on beta-dystroglycan by protein overlay and co-precipita tion assays with skeletal muscle dystrophin and recombinant apo-dystro phin I. We demonstrate that the beta-dystroglycan carboxyl terminus in teracts with dystrophin and that the binding site is restricted to the last 20 amino acids. Our data also suggest that the region adjacent t o the beta-dystroglycan transmembrane domain might modulate beta-dystr oplycan-dystrophin interaction. (C) 1996 Academic Press, Inc.