TARP亚型以剂量依赖的方式差异性地控制突触AMPA受体门控。
TARP subtypes differentially and dose-dependently control synaptic AMPA receptor gating.
作者信息
Milstein Aaron D, Zhou Wei, Karimzadegan Siavash, Bredt David S, Nicoll Roger A
机构信息
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94143, USA.
出版信息
Neuron. 2007 Sep 20;55(6):905-18. doi: 10.1016/j.neuron.2007.08.022.
Abstract
A family of transmembrane AMPA receptor regulatory proteins (TARPs) profoundly affects the trafficking and gating of AMPA receptors (AMPARs). Although TARP subtypes are differentially expressed throughout the CNS, it is unclear whether this imparts functional diversity to AMPARs in distinct neuronal populations. Here, we examine the effects of each TARP subtype on the kinetics of AMPAR gating in heterologous cells and in neurons. We report a striking heterogeneity in the effects of TARP subtypes on AMPAR deactivation and desensitization, which we demonstrate controls the time course of synaptic transmission. In addition, we find that some TARP subtypes dramatically slow AMPAR activation kinetics. Synaptic AMPAR kinetics also depend on TARP expression level, suggesting a variable TARP/AMPAR stoichiometry. Analysis of quantal synaptic transmission in a TARP gamma-4 knockout (KO) mouse corroborates our expression data and demonstrates that TARP subtype-specific gating of AMPARs contributes to the kinetics of native AMPARs at central synapses.
摘要
跨膜AMPA受体调节蛋白（TARP）家族对AMPA受体（AMPAR）的转运和门控有深远影响。尽管TARP亚型在整个中枢神经系统中差异表达，但尚不清楚这是否会赋予不同神经元群体中的AMPAR功能多样性。在这里，我们研究了每种TARP亚型对异源细胞和神经元中AMPAR门控动力学的影响。我们报告了TARP亚型对AMPAR失活和脱敏作用的显著异质性，我们证明这控制了突触传递的时间进程。此外，我们发现一些TARP亚型显著减慢了AMPAR的激活动力学。突触AMPAR动力学也取决于TARP表达水平，这表明TARP/AMPAR化学计量比是可变的。对TARP γ-4基因敲除（KO）小鼠的量子突触传递分析证实了我们的表达数据，并表明AMPAR的TARP亚型特异性门控作用有助于中枢突触处天然AMPAR的动力学。
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