Brenner H R, Witzemann V, Sakmann B
Physiologisches Institut, Universität Basel, Switzerland.
Nature. 1990 Apr 5;344(6266):544-7. doi: 10.1038/344544a0.
IN mammalian muscle, the subunit composition of the nicotinic acetylcholine receptor (AChR) and the distribution of AChRs along the fibre are developmentally regulated. In fetal muscle, AChRs are distributed over the entire fibre length whereas in adult fibres they are concentrated at the end-plate. We have used in situ hybridization techniques to measure the development of the synaptic localization of the messenger RNAs (mRNAs) encoding the alpha-subunit and the epsilon-subunit of the rat muscle AChR. The alpha-subunit is present in both fetal and adult muscle, whereas the epsilon-subunit appears postnatally and specifies the mature AChR subtype. The synaptic localization of alpha-subunit mRNA in adult fibres may arise from the selective down-regulation of constitutively expressed mRNA from extrasynaptic fibre segments. In contrast, epsilon-subunit mRNA appears locally at the site of neuromuscular contact and its accumulation at the end-plate is not dependent on the continued presence of the nerve terminal very early during synapse formation. This suggests that epsilon-subunit mRNA expression is induced locally via a signal which is restricted to the end-plate region and is dependent on the presence of the nerve only during a short period of early neuromuscular contact. Evidently, several mechanisms operate to confine AChR mRNAs to the adult end-plate region, and the levels of alpha-subunit and epsilon-subunit mRNAs depend on these mechanisms to differing degrees.
在哺乳动物肌肉中，烟碱型乙酰胆碱受体（AChR）的亚基组成以及AChR沿肌纤维的分布受到发育调控。在胎儿肌肉中，AChR分布于整个肌纤维长度，而在成年肌纤维中，它们集中在终板处。我们已使用原位杂交技术来检测编码大鼠肌肉AChRα亚基和ε亚基的信使核糖核酸（mRNA）的突触定位的发育情况。α亚基在胎儿和成年肌肉中均存在，而ε亚基在出生后出现并确定成熟的AChR亚型。成年肌纤维中α亚基mRNA的突触定位可能源于突触外肌纤维段组成型表达的mRNA的选择性下调。相比之下，ε亚基mRNA在神经肌肉接触部位局部出现，并且其在终板处的积累在突触形成的很早阶段并不依赖于神经末梢的持续存在。这表明ε亚基mRNA表达是通过一种仅限于终板区域的信号局部诱导的，并且仅在早期神经肌肉接触的短时间内依赖于神经的存在。显然，有几种机制起作用将AChR mRNA限制在成年终板区域，并且α亚基和ε亚基mRNA的水平在不同程度上依赖于这些机制。
