Schwenk Jochen, Harmel Nadine, Zolles Gerd, Bildl Wolfgang, Kulik Akos, Heimrich Bernd, Chisaka Osamu, Jonas Peter, Schulte Uwe, Fakler Bernd, Klöcker Nikolaj
Institute of Physiology II, University of Freiburg, Engesserstrasse 4, 79108 Freiburg, Germany.
Science. 2009 Mar 6;323(5919):1313-9. doi: 10.1126/science.1167852.
Glutamate receptors of the AMPA-subtype (AMPARs), together with the transmembrane AMPAR regulatory proteins (TARPs), mediate fast excitatory synaptic transmission in the mammalian brain. Here, we show by proteomic analysis that the majority of AMPARs in the rat brain are coassembled with two members of the cornichon family of transmembrane proteins, rather than with the TARPs. Coassembly with cornichon homologs 2 and 3 affects AMPARs in two ways: Cornichons increase surface expression of AMPARs, and they alter channel gating by markedly slowing deactivation and desensitization kinetics. These results demonstrate that cornichons are intrinsic auxiliary subunits of native AMPARs and provide previously unknown molecular determinants for glutamatergic neurotransmission in the central nervous system.
α-氨基-3-羟基-5-甲基-4-异恶唑丙酸亚型谷氨酸受体（AMPARs）与跨膜AMPAR调节蛋白（TARPs）共同介导哺乳动物大脑中的快速兴奋性突触传递。在此，我们通过蛋白质组学分析表明，大鼠大脑中的大多数AMPARs与跨膜蛋白的corne ichon家族的两个成员共同组装，而不是与TARPs。与corne ichon同源物2和3共同组装以两种方式影响AMPARs：corne ichons增加AMPARs的表面表达，并通过显著减慢失活和脱敏动力学来改变通道门控。这些结果表明，corne ichons是天然AMPARs的内在辅助亚基，并为中枢神经系统中的谷氨酸能神经传递提供了先前未知的分子决定因素。
