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首页> 外文期刊>Neuron >Clptm1 Limits Forward Trafficking of GABA(A) Receptors to Scale Inhibitory Synaptic Strength
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Clptm1 Limits Forward Trafficking of GABA(A) Receptors to Scale Inhibitory Synaptic Strength

机译：CLPTM1限制了向前贩运GABA（A）受体以规模抑制突触强度

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摘要

In contrast with numerous studies of glutamate receptor-associated proteins and their involvement in the modulation of excitatory synapses, much less is known about mechanisms controlling postsynaptic GABA(A) receptor (GABA(A)R) numbers. Using tandem affinity purification from tagged GABA(A)R gamma 2 subunit transgenic mice and proteomic analysis, we isolated several GABA(A) R-associated proteins, including Cleft lip and palate transmembrane protein 1 (Clptm1). Clptml interacted with all GABA(A)R subunits tested and promoted GABA(A)R trapping in the endoplasmic reticulum. Overexpression of Clptm1 reduced GABA(A)R-mediated currents in a recombinant system, in cultured hippocampal neurons, and in brain, with no effect on glycine or AMPA receptor-mediated currents. Conversely, knockdown of Clptm1 increased phasic and tonic inhibitory transmission with no effect on excitatory synaptic transmission. Furthermore, altering the expression level of Clptm1 mimicked activity-induced inhibitory synaptic scaling. Thus, in complement to other GABA(A) R-associated proteins that promote receptor surface expression, Clptm1 limits GABA(A)R forward trafficking and regulates inhibitory homeostatic plasticity.
机译：相反，与谷氨酸受体相关蛋白的许多研究及其参与调节兴奋性突触的调节，关于控制突触后GABA（A）受体的机制（GABA（A）R）数而众所周知。使用Tandem亲和纯化从标记的GABA（A）Rγ2亚基转基因小鼠和蛋白质组学分析，我们分离出几种GABA（A）R相关蛋白质，包括唇裂和腭跨膜蛋白1（CLPTM1）。 CLPTML与所有GABA（A）R亚单位相互作用，并促进内质网的GABA（A）r俘获。 CLPTM1的过度表达1减少了GABA（A）R型介导的重组系统中的电流，在培养的海马神经元和大脑中，对甘氨酸或AMPA受体介导的电流没有影响。相反，CLPTM1的敲低增加了阶段和补品抑制速度，对兴奋性突触传输没有影响。此外，改变CLPTM1模拟活性诱导的抑制突触缩放的表达水平。因此，在促进受受体表面表达的其他GABA（A）R相关蛋白质中，CLPTM1限制GABA（a）r逆转录贩运和调节抑制性稳态可塑性。

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  • 来源
    《Neuron》 |2018年第3期|共23页
  • 作者

    Ge Yuan; Kang Yunhee; Cassidy Robert M.; Moon Kyung-Mee; Lewis Renate; Wong Rachel O. L.; Foster Leonard J.; Craig Ann Marie;

  • 作者单位

    Univ British Columbia Djavad Mowafaghian Ctr Brain Hlth Vancouver BC V6T 2B5 Canada;

    Univ British Columbia Djavad Mowafaghian Ctr Brain Hlth Vancouver BC V6T 2B5 Canada;

    Univ British Columbia Djavad Mowafaghian Ctr Brain Hlth Vancouver BC V6T 2B5 Canada;

    Univ British Columbia Dept Biochem &

    Mol Biol Vancouver BC V6T 1Z3 Canada;

    Washington Univ Dept Anat &

    Neurobiol St Louis MO 63110 USA;

    Univ Washington Dept Biol Struct Seattle WA 98195 USA;

    Univ British Columbia Dept Biochem &

    Mol Biol Vancouver BC V6T 1Z3 Canada;

    Univ British Columbia Djavad Mowafaghian Ctr Brain Hlth Vancouver BC V6T 2B5 Canada;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 神经病学;
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