Na+/K+ ATPase regulates the expression and localization of acetylcholine receptors in a pump activity-independent manner
Na+/K+ ATPase regulates the expression and localization of acetylcholine receptors in a pump activity-independent manner
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DOI：
10.1016/j.mcn.2008.05.003
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发表时间：
2008-08-01
影响因子：
3.5
通讯作者：
Iwasaki, Kouichi
中科院分区：
文献类型：
--
作者：
Doi, Motomichi;Iwasaki, Kouichi
Na+/K+ ATP酶是一种位于质膜上的钠泵，它维持细胞外和细胞内环境之间的离子梯度，进而控制细胞静息膜电位。最近的证据表明，该泵也定位于突触并调节突触功效。然而，它在突触中的确切功能尚不清楚。在这里，我们表明，在秀丽隐杆线虫eat-6 Na+/K+ ATP酶的α亚基的两个突变显着增加乙酰胆碱（Ach）激动剂的敏感性，并改变神经肌肉接头（NMJ）的烟碱Ach受体的本地化。这些缺陷可以通过缺乏泵活性的突变EAT-6蛋白来挽救，这表明Ach信号传导的新功能的存在。Na+/K+ ATP酶在突触后部位聚集，并似乎包围Ach受体，以维持NMJ处的刚性簇。我们的研究结果表明，泵活性独立，等位基因特异性作用的Na+/K+ ATP酶突触后组织和突触的效力。(C)2008年爱思唯尔公司All rights reserved.
Na+/K+ ATPase is a plasma membrane-localized sodium pump that maintains the ion gradients between the extracellular and intracellular environments, which in turn controls the cellular resting membrane potential. Recent evidence suggests that the pump is also localized at synapses and regulates synaptic efficacy. However, its precise function at the synapse is unknown. Here we show that two mutations in the alpha subunit of the eat-6 Na+/K+ ATPase in Caenorhabditis elegans dramatically increase the sensitivity to acetylcholine (Ach) agonists and alter the localization of nicotinic Ach receptors at the neuromuscular junction (NMJ). These defects can be rescued by mutated EAT-6 proteins which lack its pump activity, suggesting the presence of a novel function for Ach signaling. The Na+/K+ ATPase accumulates at postsynaptic sites and appears to surround Ach receptors to maintain rigid clusters at the NMJ. Our findings suggest a pump activity-independent, allele-specific role for Na+/K+ ATPase on postsynaptic organization and synaptic efficacy. (C) 2008 Elsevier Inc. All rights reserved.