LARGE enzyme activity deciphered: a new therapeutic target for muscular dystrophies

摘要

A significant proportion of severe, inherited congenital muscular dystrophies are due to aberrant glycosylation of the extracellular matrix receptor α-dystroglycan and a consequent lack of ligand-binding activity. A key member of this glycosylation pathway is the LARGE protein, which was originally identified through genome sequencing and genetic studies. Until recently, the biochemical activity of this enzyme proved frustratingly elusive, but a recent study shows that LARGE encodes a bifunctional glycosyltransferase that synthesizes a novel polysaccharide structure, which is required for functional dystroglycan. Identification of this structure should lead to development of new diagnostic tools and therapeutic strategies for these dystrophies.