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首页> 外文期刊>Neuron >AMPA receptor subunit-specific regulation by a distinct family of type II TARPs.
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AMPA receptor subunit-specific regulation by a distinct family of type II TARPs.

机译:AMPA受体亚基的特异性调节由II型TARP的不同家族组成。

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AMPA-type glutamate receptors (GluRs) play major roles in excitatory synaptic transmission. Neuronal AMPA receptors comprise GluR subunits and transmembrane AMPA receptor regulatory proteins (TARPs). Previous studies identified five mammalian TARPs, gamma-2 (or stargazin), gamma-3, gamma-4, gamma-7, and gamma-8, that enhance AMPA receptor function. Here, we classify gamma-5 as a distinct class of TARP that modulates specific GluR2-containing AMPA receptors and displays properties entirely dissimilar from canonical TARPs. Gamma-5 increases peak currents and decreases the steady-state currents selectively from GluR2-containing AMPA receptors. Furthermore, gamma-5 increases rates of GluR2 deactivation and desensitization and decreases glutamate potency. Remarkably, all effects of gamma-5 require editing of GluR2 mRNA. Unlike other TARPs, gamma-5 modulates GluR2 without promoting receptor trafficking. We also find that gamma-7 regulation of GluR2 is dictated by mRNA editing. These data establish gamma-5 and gamma-7 as a separate family of "type II TARPs" that impart distinct physiological features to specific AMPA receptors.
机译:AMPA型谷氨酸受体(GluR)在兴奋性突触传递中起主要作用。神经元AMPA受体包含GluR亚基和跨膜AMPA受体调节蛋白(TARP)。先前的研究确定了五种哺乳动物TARP,即gamma-2(或stargazin),gamma-3,gamma-4,gamma-7和gamma-8,它们可以增强AMPA受体的功能。在这里,我们将gamma-5归类为TARP的独特类别,它可以调节特定的含GluR2的AMPA受体,并显示出与典型TARP完全不同的性质。 Gamma-5会从包含GluR2的AMPA受体中选择性地增加峰值电流,并降低稳态电流。此外,γ-5增加了GluR2失活和脱敏的速率,并降低了谷氨酸的效力。值得注意的是,γ-5的所有作用都需要编辑GluR2 mRNA。与其他TARP不同,γ-5调节GluR2而不促进受体运输。我们还发现,GluR2的gamma-7调节由mRNA编辑决定。这些数据将gamma-5和gamma-7建立为“ II型TARPs”的独立家族,这些家族赋予特定的AMPA受体独特的生理特征。

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