Muscle-specific receptor tyrosine kinase (MuSK)

Muscle-specific receptor tyrosine kinase (MuSK) is a critical cell surface receptor essential for the formation and maintenance of the neuromuscular junction (NMJ). It is primarily expressed in skeletal muscle and is activated by the neural factor Agrin in complex with the Low-density lipoprotein receptor-related protein 4 (LRP4). Upon activation, MuSK orchestrates the clustering of acetylcholine receptors (AChRs) at the postsynaptic membrane, a process vital for efficient neuromuscular transmission. Mutations in the MUSK gene or the presence of autoantibodies against the MuSK protein are primary drivers of neuromuscular disorders such as Congenital Myasthenic Syndrome and MuSK-positive Myasthenia Gravis. In therapeutic contexts, MuSK is a major target for diagnostic assays and a focal point for immunosuppressive treatments in autoimmune diseases. Recent research also explores MuSK as a potential target for treating muscle atrophy and age-related neuromuscular decline by enhancing NMJ stability.

Other names

Muscle-specific kinaseMuscle-specific tyrosine-protein kinase receptorMUSKFetal muscle-specific kinase

MuSK is activated by the nerve-derived proteoglycan Agrin via the co-receptor LRP4, leading to autophosphorylation and the recruitment of downstream signaling molecules like Dok-7 to induce the clustering of acetylcholine receptors (AChRs) at the postsynaptic membrane.