PHOSPHORYLATION OF THE NICOTINIC ACETYLCHOLINE-RECEPTOR REGULATES ITS RATE OF DESENSITIZATION
PHOSPHORYLATION OF THE NICOTINIC ACETYLCHOLINE-RECEPTOR REGULATES ITS RATE OF DESENSITIZATION
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DOI：
10.1038/321774a0
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发表时间：
1986-06-19
期刊：
影响因子：
64.8
通讯作者：
HESS, GP
中科院分区：
文献类型：
--
作者：
HUGANIR, RL;DELCOUR, AH;HESS, GP
最近的研究提供了蛋白磷酸化在调节各种钾和钙通道功能中的作用的证据（综述见参考文献1，2）。由于这些离子通道尚未被分离和表征，因此尚不可能确定离子通道本身的磷酸化是否改变了它们的性质，或者是否涉及某种间接机制。相比之下，烟碱乙酰胆碱受体，一种神经递质依赖性离子通道，已被广泛表征的生化3，并已被证明是直接磷酸化4，5。该受体的磷酸化由至少三种不同的蛋白激酶（环AMP依赖性蛋白激酶、蛋白激酶C和酪氨酸特异性蛋白激酶）在七个不同的磷酸化位点上催化6 -8。然而，受体磷酸化的功能意义尚不清楚。我们现在已经研究了cAMP依赖性蛋白激酶对烟碱乙酰胆碱受体磷酸化的功能影响。我们研究了磷酸化前后纯化和重组乙酰胆碱受体的离子转运特性。我们在此报道，cAMP依赖性蛋白激酶对γ-和δ-亚基上的烟碱乙酰胆碱受体的磷酸化增加了受体的快速脱敏速率，这是一个在乙酰胆碱（ACh）存在下受体失活的过程。这些结果提供了第一个直接的证据表明，磷酸化的离子通道蛋白调节其功能，并表明，一般突触后受体的磷酸化可能发挥重要作用，突触可塑性。
Recent studies have provided evidence for a role of protein phosphorylation in the regulation of the function of various potassium and calcium channels (for reviews, see refs 1, 2). As these ion channels have not yet been isolated and characterized, it has not been possible to determine whether phosphorylation of the ion channels themselves alters their properties or whether some indirect mechanism is involved. In contrast, the nicotinic acetylcholine receptor, a neurotransmitter-dependent ion channel, has been extensively characterized biochemically3and has been shown to be directly phosphorylated4,5. The phosphorylation of this receptor is catalysed by at least three different protein kinases (cyclic AMP-dependent protein kinase, protein kinase C and a tyrosine-specific protein kinase) on seven different phosphorylation sites6–8. However, the functional significance of phosphorylation of the receptor has been unclear. We have now examined the functional effects of phosphorylation of the nicotinic acetylcholine receptor by cAMP-dependent protein kinase. We investigated the ion transport properties of the purified and reconstituted acetylcholine receptor before and after phosphorylation. We report here that phosphorylation of the nicotinic acetylcholine receptor on theγ- andδ-subunits by cAMP-dependent protein kinase increases the rate of the rapid desensitization of the receptor, a process by which the receptor is inactivated in the presence of acetylcholine (ACh). These results provide the first direct evidence that phosphorylation of an ion channel protein modulates its function and suggest that phosphorylation of postsynaptic receptors in general may play an important role in synaptic plasticity.