dystroglycan

Dystroglycan is a cell-surface protein complex produced from the DAG1 gene that is cleaved into two subunits: alpha-dystroglycan and beta-dystroglycan. The alpha subunit is extracellular and heavily glycosylated, whereas the beta subunit is a transmembrane protein with a cytoplasmic domain. Together, they form a link between the extracellular matrix and the cytoskeleton.

Functionally, dystroglycan is a central component of the dystrophin-glycoprotein complex (DGC), which connects the basement membrane to the intracellular cytoskeleton. This linkage helps stabilize the sarcolemma during muscle contraction and may play a role in signaling. The interaction of alpha-dystroglycan with extracellular matrix ligands such as laminin, agrin, and perlecan depends on its glycosylation state; proper glycosylation enables ligand binding, while defects disrupt these interactions. Beta-dystroglycan anchors to the intracellular components of the DGC, connecting to dystrophin and related proteins.

Clinical significance arises from defects in dystroglycan or in the enzymes that glycosylate alpha-dystroglycan, leading to dystroglycanopathies. These disorders span a spectrum from mild to severe muscular dystrophy with brain and eye involvement. Congenital conditions such as Walker-Warburg syndrome and muscle-eye-brain disease illustrate the range. Mutations in genes encoding glycosyltransferases (for example, POMT1/2, POMGNT1, FKTN, FKRP, LARGE) can impair glycosylation and reduce ECM binding, contributing to disease.

Research uses include studying muscle and nervous system development, and Dag1 mouse models help illuminate the role of dystroglycan in basement membrane integrity and tissue architecture.