Motomura Masakatsu, Fukuda Taku, Yoshimura Toshiro, Tsujihata Mitsuhiro
The First Department of Internal Medicine, Graduate School of Biomedical Sciences, Nagasaki University.
Nihon Rinsho. 2008 Jun;66(6):1140-8.
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.
在突触形成过程中，肌肉特异性激酶（MuSK）/ Dok-7介导乙酰胆碱受体（AChR）的聚集，并在成熟的神经肌肉接头处表达。这些蛋白质与重症肌无力（MG）和先天性肌无力综合征（CMS）密切相关。与抗AChR抗体的MG患者相比，抗肌肉特异性酪氨酸激酶（MuSK）抗体的患者更易出现眼咽肌无力而非肢体无力、肌无力危象和肌肉萎缩。无一例有胸腺瘤，因此应研究胸腺切除术的适应证。MuSK抗体似乎不会引起补体介导的形态学运动终板损伤，但它们如何引起肌无力症状尚不清楚。结果，目前以已知抗体靶点为特征的三种类型的MG被分为：1）抗AChR抗体阳性；2）抗MuSK抗体阳性；3）上述抗体均为阴性的双血清阴性型。2006年，发现了一种名为Dok-7的与MuSK相互作用的胞质蛋白。随后，确定了Dok-7的突变是CMS的病因，这为Dok-7在维持突触结构中的关键作用提供了证据。它们对MuSK / Dok-7功能的影响有待探索。
