Upon activation by its ligand agrin, MuSK signals via the proteins called Casein kinase 2 (CK2),Dok-7 and rapsyn, to induce "clustering" of acetylcholine receptors (AChR). Both CK2 and Dok-7 are required for MuSK-induced formation of the neuromuscular junction, since mice lacking Dok-7 failed to form AChR clusters or neuromuscular synapses, and since downregulation of CK2 also impedes recruitment of AChR to the primary MuSK scaffold. In addition to the proteins mentioned, other proteins are then gathered, to form the endplate to the neuromuscular junction. The nerve terminates onto the endplate, forming the neuromuscular junction - a structure required to transmit nerve impulses to the muscle, and thus initiating muscle contraction.
Antibodies directed against this protein (Anti-MuSK autoantibodies) are found in those patients with myasthenia gravis not demonstrating antibodies to the acetylcholine receptor (sero-negative). The disease still appears to result in an autoimmune loss of acetylcholine receptor activity, but the phenotype of these patients appears to be different from those of many other myasthenic patients: more likely women, less eye involvement, more likely to have weakness of neck and oropharynx, and more likely to be African-American in ethnicity. In preclinical models of anti-MuSK myasthenia gravis, administration of 3,4-diaminopyridine increases the release of acetylcholine in the neuromuscular junction and reduces muscle weakness.
^Hoch W, McConville J, Helms S, Newsom-Davis J, Melms A, Vincent A (Mar 2001). "Auto-antibodies to the receptor tyrosine kinase MuSK in patients with myasthenia gravis without acetylcholine receptor antibodies". Nature Medicine7 (3): 365–8. doi:10.1038/85520. PMID11231638.
^Barrett-Jolley R, Byrne N, Vincent A, Newsom-Davis J (Oct 1994). "Plasma from patients with seronegative myasthenia gravis inhibit nAChR responses in the TE671/RD cell line". Pflügers Archiv428 (5-6): 492–8. doi:10.1007/BF00374570. PMID7838671.
^Morsch M, Reddel SW, Ghazanfari N, Toyka KV, Phillips WD (May 2013). "Pyridostigmine but not 3,4-diaminopyridine exacerbates ACh receptor loss and myasthenia induced in mice by muscle-specific kinase autoantibody". The Journal of Physiology591 (Pt 10): 2747–62. doi:10.1113/jphysiol.2013.251827. PMID23440963.