Agrin [MD350]

Agrin is a molecule that resides in the basal lamina of muscle cells and directs key events in post synaptic differentiation. It is an essential extracellular matrix component which promotes clustering of nicotinic acetylcholine receptors (nAChRs) on the cell surface and their localization to the neuromuscular junction.. Agrin, MuSK and Rapsyn are all essential components for AChR aggregation, through an unknown mechanism. The C-terminal region of agrin is released into the medium, interacts with receptors on the muscle surface and induces AChR aggregation. The central region contains two O-linked glycosylation sites and a domain homologous to domain III of laminin. The N-terminal region anchors agrin to the extracellular matrix via other basal membrane components. Muscle alpha-dystroglycan has been postulated to be the receptor for the clustering activity of agrin; however, this is a point of contention. Tyrosine phosphorylation has been implicated as a required early step in AChR aggregation. Interestingly, a unique receptor tyrosine kinase, designated MuSK, has been discovered that interacts with Agrin and is specifically localized to developing muscle.