Muscle cell surface glycans and associated receptors

Muscle cell surface glycans and associated receptors constitute a complex system of carbohydrate modifications and their corresponding protein or lipid scaffolds on the sarcolemma of muscle fibers. These glycans, such as sialic acid, galactose, and mannose-6-phosphate, play vital roles in maintaining membrane stability, facilitating cell-matrix interactions, and serving as signaling hubs (NIH, 2021). A prominent example is the dystroglycan complex, where alpha-dystroglycan requires specific O-mannosyl glycans to bind extracellular matrix proteins like laminin (PubMed, 2004). In GNE myopathy, mutations in the sialic acid biosynthetic pathway lead to the hyposialylation of these glycans, causing progressive muscle degeneration (NIH, 2021). Additionally, these glycans and their associated protein receptors, such as the adeno-associated virus receptor (AAVR), are the primary targets for the attachment and entry of adeno-associated virus (AAV) vectors used in gene therapies for muscular dystrophies (PubMed, 2019). Therapeutic strategies include the use of glycan precursors like N-acetylmannosamine (ManNAc) to restore sialylation or the engineering of AAV capsids to optimize binding to specific muscle surface glycan profiles. Enzyme replacement therapies, such as those for Pompe disease, also utilize specific glycans like mannose-6-phosphate for targeted uptake into muscle cells via the cation-independent mannose-6-phosphate receptor.

Other names

Muscle glycocalyxSialylated muscle glycoproteinsDystroglycan-associated glycansMuscle cell surface carbohydratesHereditary inclusion body myopathy (HIBM) associated glycansNonaka myopathy associated glycans

Restoration of glycan sialylation through substrate supplementation; viral vector attachment to cell surface glycans followed by protein-mediated internalization; receptor-mediated endocytosis for enzyme delivery.