Porcupine Controls Hippocampal AMPAR Levels, Composition, and Synaptic Transmission.
Porcupine Controls Hippocampal AMPAR Levels, Composition, and Synaptic Transmission.
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DOI：
10.1016/j.celrep.2015.12.078
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发表时间：
2016-02-02
期刊：
影响因子：
8.8
通讯作者：
Bredt DS
中科院分区：
文献类型：
--
作者：
Erlenhardt N;Yu H;Abiraman K;Yamasaki T;Wadiche JI;Tomita S;Bredt DS
AMPAR （AMPAR）复合物含有辅助亚基，可调节受体转运和门控。除了跨膜AMPAR调节蛋白（TARPs）和角状子（CNIH-2/3）外，最近的蛋白质组学研究还发现了一系列其他与AMPAR相关的跨膜和分泌伙伴。我们系统地调查了这些，发现PORCN和ABHD6增加了转染细胞中的GluA1水平。在大量表达PORCN的大鼠海马神经元中，敲低PORCN可选择性地降低所有测试的AMPAR复合物组分的水平。AMPARs的调控与PORCN膜相关的o -酰基转移酶活性无关。海马神经元中PORCN敲低降低AMPAR电流，加速脱敏，导致TARP γ-8从AMPAR复合物中耗损。条件PORCN敲除小鼠也表现出AMPAR表达和门控的特异性变化，减少基础突触传递，但保持长期增强完整。这些研究确定了PORCN通过调节海马AMPAR复合物的水平和组成来控制突触传递的其他作用。
AMPAR (AMPAR) complexes contain auxiliary subunits that modulate receptor trafficking and gating. In addition to the transmembrane AMPAR regulatory proteins (TARPs) and cornichons (CNIH-2/3), recent proteomic studies identified a diverse array of additional AMPAR-associated transmembrane and secreted partners. We systematically surveyed these and found that PORCN and ABHD6 increase GluA1 levels in transfected cells. Knockdown of PORCN in rat hippocampal neurons, which express it in high amounts, selectively reduces levels of all tested AMPAR complex components. Regulation of AMPARs is independent of PORCN’s membrane-associated O-acyl transferase activity. PORCN knockdown in hippocampal neurons decreases AMPAR currents and accelerates desensitization, and leads to depletion of TARP γ-8 from AMPAR complexes. Conditional PORCN knockout mice also exhibit specific changes in AMPAR expression and gating that reduce basal synaptic transmission, but leave long-term potentiation intact. These studies define additional roles for PORCN in controlling synaptic transmission by regulating the level and composition of hippocampal AMPAR complexes.