Metabotropic glutamate receptor-mediated LTD involves two interacting Ca(2+) sensors, NCS-1 and PICK1.

Metabotropic glutamate receptor-mediated LTD involves two interacting Ca(2+) sensors, NCS-1 and PICK1.
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DOI:
10.1016/j.neuron.2008.10.050
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发表时间:
2008-12-26
期刊:
影响因子:
16.2
通讯作者:
Cho, Kwangwook
Cho, Kwangwook
中科院分区:
医学1区
文献类型:
--
作者:
Jo, Jihoon;Heon, Seok;Kim, Myung Jong;Son, Gi Hoon;Park, Yunkyung;Henley, Jeremy M.;Weiss, Jamie L.;Sheng, Morgan;Collingridge, Graham L.;Cho, Kwangwook

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中枢神经系统突触传递的长期抑制(LTD)主要有两种形式,需要激活n -甲基- d -天冬氨酸受体(NMDARs)或代谢性谷氨酸受体(mGluRs)。在周围皮层突触中,我们直接比较了NMDAR-LTD和mGluR-LTD所涉及的Ca2+信号传导机制。虽然两种形式的LTD都涉及细胞内储存的Ca2+释放,但涉及的Ca2+传感器是不同的;NMDAR-LTD涉及钙调蛋白,而mGluR-LTD涉及神经元Ca2+传感器(NCS)蛋白NCS-1。此外,mGluR-LTD对IP3和PKC以及与C激酶(PICK-1)相互作用的蛋白也有特殊的需求。NCS-1通过其BAR结构域以Ca2+依赖的方式直接与PICK1结合。此外,NCS-1-PICK1关联可通过mGluRs激活而非NMDARs激活,并且PICK1 BAR结构域融合蛋白的引入特异性地阻断mGluR-LTD。因此,NCS-1在mGluR-LTD中起着独特的作用。
There are two major forms of long-term depression (LTD) of synaptic transmission in the central nervous system that require activation of either N-methyl-D-aspartate receptors (NMDARs) or metabotropic glutamate receptors (mGluRs). In synapses in the perirhinal cortex, we have directly compared the Ca2+ signaling mechanisms involved in NMDAR-LTD and mGluR-LTD. While both forms of LTD involve Ca2+ release from intracellular stores, the Ca2+ sensors involved are different; NMDAR-LTD involves calmodulin, while mGluR-LTD involves the neuronal Ca2+ sensor (NCS) protein NCS-1. In addition, there is a specific requirement for IP3 and PKC, as well as protein interacting with C kinase (PICK-1) in mGluR-LTD. NCS-1 binds directly to PICK1 via its BAR domain in a Ca2+-dependent manner. Furthermore, the NCS-1-PICK1 association is stimulated by activation of mGluRs, but not NMDARs, and introduction of a PICK1 BAR domain fusion protein specifically blocks mGluR-LTD. Thus, NCS-1 plays a distinct role in mGluR-LTD.
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