Electrophysiological properties of AMPA receptors are differentially modulated depending on the associated member of the TARP family
Electrophysiological properties of AMPA receptors are differentially modulated depending on the associated member of the TARP family
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DOI：
10.1523/jneurosci.4185-06.2007
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发表时间：
2007-04-04
影响因子：
5.3
通讯作者：
Hollmann, Michael
中科院分区：
文献类型：
--
作者：
Kott, Sabine;Werner, Markus;Hollmann, Michael
AMPA受体家族由四个基因编码，这些基因被差异剪接以产生四个亚基GluR 1至GluR 4的翻转或翻转版本。GluR 2通过转录后RNA编辑在所谓的Q/R位点进一步修饰。跨膜AMPA受体调节蛋白（TARP）控制AMPA受体向质膜的传递和突触运输。此外，TARPs影响AMPA受体通道的基本电生理特性，如脱敏和激动剂功效。在这里，我们比较了所有已知的TARP（γ 2，γ 3，γ 4和γ 8）对激动剂诱导的电流的四个AMPA受体亚基，包括翻转和翻转剪接变体和编辑变体的影响。我们表明，虽然激动剂诱导的电流的所有同源AMPA受体亚基以及所有异聚体组合测试显着增强时，与非洲爪蟾卵母细胞中的TARP家族的成员共表达，TARP介导的激动剂诱导的反应的增加的程度是高度依赖于AMPA受体亚基和共表达的TARP。此外，我们证明了AMPA受体的剪接变体在确定相关TARPs对电生理特性的调制中起着关键作用。此外，我们提出的证据表明，个别TARP-AMPA受体相互作用控制AMPA受体的脱敏程度。因此，由于它们对电生理特性的亚基特异性影响，TARPs作为AMPA受体的调节亚基发挥主要作用，从而有助于CNS中遇到的AMPA受体的功能多样性。
The family of AMPA receptors is encoded by four genes that are differentially spliced to result in the flip or flop versions of the four subunits GluR1 to GluR4. GluR2 is further modified at the so- called Q/R site by posttranscriptional RNA editing. Delivery of AMPA receptors to the plasma membrane and synaptic trafficking are controlled by transmembrane AMPA receptor regulatory proteins (TARPs). Additionally, TARPs influence essential electrophysiological properties of AMPA receptor channels such as desensitization and agonist efficacies. Here, we compare the influence of all known TARPs (gamma 2, gamma 3, gamma 4, and gamma 8) on agonist-induced currents of the four AMPA receptor subunits, including flip and flop splice variants and editing variants. We show that, although agonist- induced currents of all homomeric AMPA receptor subunits as well as all heteromeric combinations tested are significantly potentiated when coexpressed with members of the TARP family in Xenopus laevis oocytes, the extent of TARP-mediated increase in agonist- induced responses is highly dependent on both the AMPA receptor subunit and the coexpressed TARP. Moreover, we demonstrate that the splice variant of the AMPA receptor plays a key role in determining the modulation of electrophysiological properties by associated TARPs. We furthermore present evidence that individual TARP-AMPA receptor interactions control the degree of desensitization of AMPA receptors. Consequently, because of their subunit-specific impact on the electrophysiological properties, TARPs play a major role as modulatory subunits of AMPA receptors and thus contribute to the functional diversity of AMPA receptors encountered in the CNS.