Rapid upregulation of α7 nicotinic acetylcholine receptors by tyrosine dephosphorylation
Rapid upregulation of α7 nicotinic acetylcholine receptors by tyrosine dephosphorylation
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DOI：
10.1523/jneurosci.5389-03.2005
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发表时间：
2005-04-06
影响因子：
5.3
通讯作者：
Lester, RAJ
中科院分区：
文献类型：
--
作者：
Cho, CH;Song, WF;Lester, RAJ
α 7烟碱乙酰胆碱受体（nAChR）调节CNS中的网络活性。因此，α 7 nAChRs的功能调节可以影响通过各种脑核团的信息流。这里假设这些受体可通过酪氨酸磷酸化进行调节。在非洲爪蟾卵母细胞和大鼠海马中间神经元，短暂暴露于广谱蛋白酪氨酸激酶抑制剂，染料木素，特异性和可逆性增强α 7乙酰胆碱受体介导的反应，而蛋白酪氨酸磷酸酶抑制剂，过钒酸盐，引起抑郁症。增强与表面α 7亚基表达增加相关，并且不伴随受体开放概率的可检测变化，这意味着功能增加是由于α 7 nAChR数量增加所致。可溶性N-乙基马来酰亚胺敏感因子附着蛋白受体介导的胞吐作用被证明是将额外的α 7 nAChR快速递送至质膜的合理机制。α 7亚基的直接磷酸化/去磷酸化是不可能的，因为所有三个胞质酪氨酸残基的突变并不能阻止染料木素介导的促进作用。总的来说，这些数据与功能性细胞表面α 7 nAChR的数量通过涉及酪氨酸磷酸化的过程间接控制的假设一致。
alpha 7 nicotinic acetylcholine receptors (nAChRs) modulate network activity in the CNS. Thus, functional regulation of alpha 7 nAChRs could influence the flow of information through various brain nuclei. It is hypothesized here that these receptors are amenable to modulation by tyrosine phosphorylation. In both Xenopus oocytes and rat hippocampal interneurons, brief exposure to a broad-spectrum protein tyrosine kinase inhibitor, genistein, specifically and reversibly potentiated alpha 7 nAChR-mediated responses, whereas a protein tyrosine phosphatase inhibitor, pervanadate, caused depression. Potentiation was associated with an increased expression of surface alpha 7 subunits and was not accompanied by detectable changes in receptor open probability, implying that the increased function results from an increased number of alpha 7 nAChRs. Soluble N-ethylmaleimide-sensitive factor attachment protein receptor-mediated exocytosis was shown to be a plausible mechanism for the rapid delivery of additional alpha 7 nAChRs to the plasma membrane. Direct phosphorylation/ dephosphorylation of alpha 7 subunits was unlikely because mutation of all three cytoplasmic tyrosine residues did not prevent the genisteinmediated facilitation. Overall, these data are consistent with the hypothesis that the number of functional cell surface alpha 7 nAChRs is controlled indirectly via processes involving tyrosine phosphorylation.