EM.P.2.01 Expression analysis of α-dystroglycan glycosyltransferases during myoblast-myotube differentiation

Abstract

The dystroglycanopathies are a group of muscular dystrophies that share the common pathological feature of a hypoglycosylated form of α-dystroglycan. To date six known or putative glycosyltransferase enzymes have been found to underlie these disorders: Protein-O-mannosyl transferase 1 (POMT1), Protein-O-mannosyl transferase 2 (POMT2), Protein-O-mannose 1,2-N-acetylglucosaminyltransferase 1 (POMGnT1), Fukutin, Fukutin-related protein (FKRP) and LARGE. Dystroglycan is a component of the dystrophin-associated glycoprotein complex present at the skeletal muscle sarcolemma. The α-subunit is a heavily glycosylated peripheral membrane protein that has tissue specific and developmental patterns of O-glycosylation, some of which are rare O-mannosyl glycans whose synthesis is initiated by POMT1, POMT2 and POMGnT1. The functions of the remaining enzymes in the glycosylation of α-dystroglycan are unknown, although there is strong evidence that LARGE plays a pivotal role.