TARP redundancy is critical for maintaining AMPA receptor function
TARP redundancy is critical for maintaining AMPA receptor function
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DOI：
10.1523/jneurosci.1319-08.2008
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发表时间：
2008-08-27
影响因子：
5.3
通讯作者：
Nicoll, Roger A.
中科院分区：
文献类型：
--
作者：
Menuz, Karen;O'Brien, Jessica L.;Nicoll, Roger A.
跨膜AMPA受体调节蛋白（Transmembrane AMPA receptor regulatory proteins，TARP）是AMPA受体的辅助亚基，影响受体功能的各个方面。然而，完整的补充，在体内的生理作用的TARP仍然知之甚少。在这里，我们发现缺乏TARP γ-2和γ-3的双敲除小鼠严重共济失调，无法茁壮成长。我们证明，这些TARP是至关重要的突触靶向和动力学的AMPA受体在小脑高尔基体细胞，但无论是单独足以完全保留功能。通过分析γ-2、γ-3双基因敲除小鼠中少数剩余的突触AMPA受体，我们意外地发现这些TARP指定AMPA受体亚基组成。这项研究建立了一个新的作用，TARPs在调节AMPA受体组装，并表明，TARPs是必要的适当的AMPA受体的定位和功能，在大多数，如果不是所有的，中枢神经系统的神经元。
Transmembrane AMPA receptor regulatory proteins (TARPs) are AMPA receptor auxiliary subunits that influence diverse aspects of receptor function. However, the full complement of physiological roles for TARPs in vivo remains poorly understood. Here we find that double knock-out mice lacking TARPs gamma-2 and gamma-3 are profoundly ataxic and fail to thrive. We demonstrate that these TARPs are critical for the synaptic targeting and kinetics of AMPA receptors in cerebellar Golgi cells, but that either alone is sufficient to fully preserve function. By analyzing the few remaining synaptic AMPA receptors in the gamma-2, gamma-3 double knock-out mice, we unexpectedly find that these TARPs specify AMPA receptor subunit composition. This study establishes a new role for TARPs in regulating AMPA receptor assembly and suggests that TARPs are necessary for proper AMPA receptor localization and function in most, if not all, neurons of the CNS.