MuSK protein

MuSK signaling

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.

Role in disease

Antibody Antibodies directed against this protein (Anti-MuSK autoantibodies) are found in some people with myasthenia gravis not demonstrating antibodies to the acetylcholine receptor. The disease still causes loss of acetylcholine receptor activity, but the symptoms affected people experience may differ from those of people with other causes of myasthenia gravis.

References

References

1. (Sep 1995). "Receptor tyrosine kinase specific for the skeletal muscle lineage: expression in embryonic muscle, at the neuromuscular junction, and after injury". Neuron.
2. (May 1996). "The receptor tyrosine kinase MuSK is required for neuromuscular junction formation in vivo". Cell.
3. (May 1996). "Agrin acts via a MuSK receptor complex". Cell.
4. (May 1996). "Defective neuromuscular synaptogenesis in agrin-deficient mutant mice". Cell.
5. (May 1996). "Agrin acts via a MuSK receptor complex". Cell.
6. (Jul 2006). "Casein kinase 2-dependent serine phosphorylation of MuSK regulates acetylcholine receptor aggregation at the neuromuscular junction". Genes & Development.
7. (Jun 2006). "The muscle protein Dok-7 is essential for neuromuscular synaptogenesis". Science.
8. (Mar 2001). "Auto-antibodies to the receptor tyrosine kinase MuSK in patients with myasthenia gravis without acetylcholine receptor antibodies". Nature Medicine.
9. (Oct 1994). "Plasma from patients with seronegative myasthenia gravis inhibit nAChR responses in the TE671/RD cell line". Pflügers Archiv.