Protein kinase C modulates NMDA receptor trafficking and gating
Protein kinase C modulates NMDA receptor trafficking and gating
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DOI：
10.1038/86028
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发表时间：
2001-04-01
影响因子：
25
通讯作者：
Zukin, RS
中科院分区：
文献类型：
--
作者：
Lan, JY;Skeberdis, VA;Zukin, RS
神经元N-甲基-D-天冬氨酸受体（NMDAR）通过蛋白激酶的调节在突触传递中至关重要。然而，蛋白激酶C（PKC）增强NMDAR的分子机制尚不确定。在这里，我们证明，PKC增加NMDA通道开放率，并提供新的NMDA通道，质膜通过调节胞吐。PKC诱导的功能NMDARs的快速交付到细胞表面和增加的表面NR 1在表达NMDARs的非洲爪蟾卵母细胞的免疫荧光。PKC增强被肉毒杆菌神经毒素A和可溶性NSF相关蛋白（SNAP-25）的显性负突变体抑制，表明受体转运通过SNARE依赖性胞吐作用发生。在神经元中，PKC诱导功能性NMDAR的快速递送，通过电生理学评估，以及树突和树突棘表面上NMDAR簇的增加，如免疫荧光所示。因此，PKC调节重组系统和神经元中的NMDAR通道门控和运输，其机制可能与突触可塑性相关。
Regulation of neuronal N-methyl-D-aspartate receptors (NMDARs) by protein kinases is critical in synaptic transmission. However, the molecular mechanisms underlying protein kinase C (PKC) potentiation of NMDARs are uncertain. Here we demonstrate that PKC increases NMDA channel opening rate and delivers new NMDA channels to the plasma membrane through regulated exocytosis. PKC induced a rapid delivery of functional NMDARs to the cell surface and increased surface NR1 immunofluorescence in Xenopus oocytes expressing NMDARs. PKC potentiation was inhibited by botulinum neurotoxin A and a dominant negative mutant of soluble NSF-associated protein (SNAP-25), suggesting that receptor trafficking occurs via SNARE-dependent exocytosis. In neurons, PKC induced a rapid delivery of functional NMDARs, assessed by electrophysiology, and an increase in NMDAR clusters on the surface of dendrites and dendritic spines, as indicated by immunofluorescence. Thus, PKC regulates NMDAR channel gating and trafficking in recombinant systems and in neurons, mechanisms that may be relevant to synaptic plasticity.