[Overview: MuSK/Dok-7].
MuSK/Dok-7 mediate the clustering of acetylcholine receptor (AChR) during synapse formation and are expressed at the mature neuromuscular junction. These proteins are deeply associated with myasthenia gravis (MG) and congenital myasthenic syndrome (CMS). Compared with MG patients with AChR antibodies, those with muscle-specific tyrosine kinase (MuSK) antibodies are more likely to present oculobulbar than limb weakness, myasthenic crisis and muscle wasting. None have thymoma, so the indication for thymectomy should be investigated. MuSK antibodies do not appear to cause complement-mediated morphological motor endplate damage, but how they cause myasthenic symptoms is unclear. As the results, the three types of MG presently characterized by known antibody targets are classified into 1) AChR antibody-positive, 2) MuSK antibody -positive, and 3) double seronegative type which the above-mentioned antibodies are negative. In 2006, MuSK-interacting cytoplasmic protein termed Dok-7 has been found. Subsequently, mutations in Dok-7 as a cause of CMS were identified, providing evidence for a crucial role of Dok-7 in maintaining synaptic structure. Their effect on MuSK/Dok -7 function needs to be explored.
The First Department of Internal Medicine, Graduate School of Biomedical Sciences, Nagasaki University.
Masakatsu
M
Motomura
Taku
T
Fukuda
Toshiro
T
Yoshimura
Mitsuhiro
M
Tsujihata
D004789:Enzyme Activation; D005260:Female; D006801:Humans; D008297:Male; D009124:Muscle Proteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D009157:Myasthenia Gravis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D011950:Receptors, Cholinergic / Q000235:genetics / Q000276:immunology / Q000502:physiology*
C511692:DOK7 protein, human; D009124:Muscle Proteins; D011950:Receptors, Cholinergic; C095714:MUSK protein, human; D020794:Receptor Protein-Tyrosine Kinases