Localization and regulation of MuSK at the neuromuscular junction
Localization and regulation of MuSK at the neuromuscular junction
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DOI：
10.1006/dbio.1998.8936
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发表时间：
1998-07-15
影响因子：
2.7
通讯作者：
DiStefano, PS
中科院分区：
文献类型：
--
作者：
Bowen, DC;Park, JS;DiStefano, PS
受体酪氨酸激酶 MuSK 是神经肌肉接头 (NMJ) 形成所必需的，当暴露于神经元合成的集聚蛋白亚型时，MuSK 会被磷酸化。为了更好地了解 MuSK 介导 NMJ 形成的机制，我们研究了 MuSK 表达在胚胎发育过程中、成人中的神经肌肉损伤和体外集聚蛋白是如何调节的。在这里，我们表明 MuSK 与发育中的运动终板处最早可观察到的 AChR 簇相关，并且 MuSK 和 AChR 在 NMJ 的整个发育过程中共同分布。这两种蛋白质也在培养的肌管表面受到协调调节，其中 MuSK 和 AChR 在自发簇和集聚蛋白诱导簇中共定位。虽然 MuSK 通常仅限于成人肌肉的运动终板，但去神经导致其交界外表达，尽管即使在去神经 14 天后，MuSK 的可辨别浓度仍然位于运动终板。交界外 MuSK 在去神经支配后 3 天首次出现，并在重新神经支配后急剧减少。肌肉麻痹还显着改变成人肌肉中 MuSK 的表达，导致 MuSK 表达增加以及突触外肌核的 MuSK mRNA 转录增加。总之，这些发现表明 MuSK 表达受到神经支配、肌肉活动和集聚蛋白的高度调节，而 MuSK 的分布与 AChR 的分布精确协调。 (C) 1998 年学术出版社。
The receptor tyrosine kinase, MuSK, is required for the formation of the neuromuscular junction (NMJ) where MuSK becomes phosphorylated when exposed to neuronally synthesized isoforms of agrin. To understand better the mechanisms by which MuSK mediates the formation of the NMJ, we have examined how MuSK expression is regulated during development in the embryo, by neuromuscular injury in the adult and by agrin in vitro. Here we show that MuSK is associated with the earliest observable AChR clusters at the developing motor endplate and that MuSK and AChRs codistribute throughout the development of the NMJ. These two proteins are also coordinately regulated on the surfaces of cultured myotubes where MuSK and AChRs colocalize both in spontaneous and agrin-induced clusters. While MuSK is normally restricted to the motor endplate in adult muscle, denervation results in its extrajunctional expression, although a discernible concentration of MuSK remains localized to the motor endplate even 14 days after denervation. Extrajunctional MuSK is first apparent 3 days after denervation and is sharply reduced upon reinnervation. Muscle paralysis also markedly alters the expression of MuSK in adult muscle and results in increased expression of MuSK as well as increased transcription of MuSK mRNA by extrasynaptic myonuclei. Together, these findings demonstrate that MuSK expression is highly regulated by innervation, muscle activity, and agrin, while the distribution of MuSK is precisely coordinated with that of the AChR. (C) 1998 Academic Press.