HUMAN DYSTROGLYCAN - SKELETAL-MUSCLE CDNA, GENOMIC STRUCTURE, ORIGIN OF TISSUE-SPECIFIC ISOFORMS AND CHROMOSOMAL LOCALIZATION

Dystroglycan is a novel laminin binding component of the dystrophin-gl ycoprotein complex which provides a linkage between the subsarcolemmal cytoskeleton and the extracellular matrix. Here we report the cDNA an d genomic structure of human dystroglycan. The human dystroglycan is e ncoded by a single gene (DAG1) mapped to chromosome 3 band p21. The co ding sequence is organized into two exons, separated by a large intron . The predicted amino acid sequence of human and rabbit dystroglycan a re 93% identical with predicted glycosylation sites being conserved. H uman dystroglycan is expressed in a variety of fetal and adult tissues . Our data suggest that muscle and non-muscle isoforms of dystroglycan differ by carbohydrate moieties but not protein sequence. Therefore, we hypothesize that variable glycosylation of the conserved protein co re might modulate laminin binding. The relationship of dystroglycan to human diseases is discussed.