Heparan sulfates in skeletal muscle development and physiology

Recent years have seen an emerging interest in the composition of the skeletal muscle extracellular matrix (ECM) and in the developmental and physiological roles of its constituents. Many cell surface-associated and ECM-embedded molecules occur in highly organized spatiotemporal patterns, suggesting important roles in the development and functioning of skeletal muscle. Glycans are historically underrepresented in the study of skeletal muscle ECM, even though studies from up to 30 years ago have demonstrated specific carbohydrates and glycoproteins to be concentrated in neuromuscular junctions (NMJs). Changes in glycan profile and distribution during myogenesis and synaptogenesis hint at an active involvement of glycoconjugates in muscle development. A modest amount of literature involves glycoconjugates in muscle ion housekeeping, but a recent surge of evidence indicates that glycosylation defects are causal for many congenital (neuro)muscular disorders, rendering glycosylation essential for skeletal muscle integrity. In this review, we focus on a single class of ECM-resident glycans and their emerging roles in muscle development, physiology, and pathology: heparan sulfate proteoglycans (HSPGs), notably their heparan sulfate (HS) moiety.