Antibody to acetylcholine receptor increases degradation of junctional and extrajunctional receptors in adult muscle
Antibody to acetylcholine receptor increases degradation of junctional and extrajunctional receptors in adult muscle
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DOI：
10.1038/274068a0
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发表时间：
1978-07
期刊：
影响因子：
64.8
通讯作者：
C. Reiness;Zach W. Hall;C. B. Weinberg
中科院分区：
文献类型：
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作者：
C. Reiness;Zach W. Hall;C. B. Weinberg
重症肌无力是一种神经肌肉传递受损的疾病（参见文献1），这可能是由于肌肉膜中乙酰胆碱（ACh）受体数量减少所致2。肌无力被认为是一种自身免疫性疾病，部分原因是大多数肌无力患者体内有针对受体的循环抗体3,4。在组织培养中，特异性抗体可以增加细胞的周转率，减少细胞表面蛋白5的数量，包括乙酰胆碱受体6 - 8。由于这种作用可能导致肌无力中乙酰胆碱受体的减少，我们研究了抗受体抗体对成年大鼠神经支配和去神经支配肌肉中乙酰胆碱受体转换的影响。在哺乳动物肌肉中发现了两种形式的乙酰胆碱受体。接合感受器密集分布并高度定位于运动终板9 - 11，而接合外感受器在发育和失神经成人肌肉中以低密度分布于整个肌肉表面10 - 12。这两种形式的受体几乎是相同的分子，但可以在原位和纯化后进行区分（有关讨论，参见参考文献13）。等电点14和免疫学特性的差异（参考文献15和C.B.W.和Z.W.H.未发表的结果）表明它们在结构上有轻微的差异。这些形式的受体之间的一个重要区别是它们在膜中的稳定性。在发育中的和失神经的成人肌肉中，结外受体经历持续的更新，半衰期约为14-18小时16 - 18。相比之下，连接受体更加稳定，虽然它们在体内的半衰期估计超过6天（参考文献16和18），但以前没有发现它们会翻转。我们在此报告，连接受体可以翻转，抗受体抗体增加了成人肌肉中连接和连接外受体的降解。
MYASTHENIA gravis is a disease of impaired neuromuscular transmission (for review see ref. 1), which probably results from a reduced number of acetylcholine (ACh) receptors in the muscle membrane2. Myasthenia is thought to be an autoimmune disease1, in part because most myasthenia patients have circulating antibody to the receptor3,4. Specific antibodies can increase the turnover and reduce the amount of surface proteins5, including ACh receptors6–8, on cells in tissue culture. Because such an effect could contribute to the decrease of ACh receptors found in myasthenia, we have investigated the effect of anti-receptor antibodies on the turnover of ACh receptors in innervated and denervated muscles of adult rats. Two forms of ACh receptor are found in mammalian muscle. Junctional receptors are densely packed and highly localised at motor endplates9–11, while extrajunctional receptors are found in developing and denervated adult muscles at low density over the entire muscle surface10–12. The two forms of receptors are almost identical molecules but can be distinguished bothin situand after purification (for discussion, see ref. 13). Differences in isoelectric point14and immunological properties (ref. 15 and unpublished results of C.B.W. and Z.W.H.) suggest that they have slight structural differences. One important difference between these forms of receptors is their stability in the membrane. Extrajunctional receptors undergo continual turnover with a half-life of about 14–18 h in both developing and denervated adult muscles16–18. In contrast junctional receptors are much more stable and have not previously been shown to turn over, although their half-lifein vivohas been estimated to exceed 6 d (refs 16 and 18). We report here that junctional receptors can turn over and that antireceptor antibodies increase the degradation of both junctional and extrajunctional receptors in adult muscle.