An ER-resident membrane protein complex regulates nicotinic acetylcholine receptor subunit composition at the synapse
An ER-resident membrane protein complex regulates nicotinic acetylcholine receptor subunit composition at the synapse
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DOI：
10.1038/emboj.2009.204
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发表时间：
2009-09-02
期刊：
影响因子：
11.4
通讯作者：
Gottschalk, Alexander
中科院分区：
文献类型：
--
作者：
Almedom, Ruta B.;Liewald, Jana F.;Gottschalk, Alexander
烟碱型乙酰胆碱受体（nAChR）是一种同源或异源五聚体配体门控离子通道，介导兴奋性神经传递和肌肉激活。调节nAChR亚基组装和正确组装的五聚体转移到细胞表面仅部分了解。在这里，我们表征ER跨膜（TM）蛋白复合物，影响nAChR细胞表面的表达和功能特性秀丽隐杆线虫肌肉。I型TM蛋白NRA-2或NRA-4（烟碱受体相关）的缺失影响两种不同类型的肌肉nAChR，并导致体内对胆碱能激动剂的抗性。这些nAChRs的亚型特异性激动剂的敏感性改变不同，如通过解剖的成人肌肉的全细胞电压钳，当施加外源性激动剂或光诱发后，通道视紫红质-2（ChR 2）介导的乙酰胆碱（ACh）释放，以及在培养的胚胎肌肉中的单通道记录。这些数据表明nAChR在nra-2突变体中脱敏更快。在NRA-2或NRA-4不存在的情况下，“左旋咪唑敏感”nAChR（L-AChR）的不同亚基的细胞表面表达受到不同的影响，这表明它们控制nAChR亚基的组成或仅允许某些受体组件离开ER。The EMBO Journal（2009）28，2636-2649. doi：10.1038/djj.2009.204;在线发表于2009年7月16日主题分类：膜和运输;神经科学
Nicotinic acetylcholine receptors (nAChRs) are homo- or heteropentameric ligand-gated ion channels mediating excitatory neurotransmission and muscle activation. Regulation of nAChR subunit assembly and transfer of correctly assembled pentamers to the cell surface is only partially understood. Here, we characterize an ER transmembrane (TM) protein complex that influences nAChR cell-surface expression and functional properties in Caenorhabditis elegans muscle. Loss of either type I TM protein, NRA-2 or NRA-4 (nicotinic receptor associated), affects two different types of muscle nAChRs and causes in vivo resistance to cholinergic agonists. Sensitivity to subtype-specific agonists of these nAChRs is altered differently, as demonstrated by whole-cell voltage-clamp of dissected adult muscle, when applying exogenous agonists or after photo-evoked, channelrhodopsin-2 (ChR2) mediated acetylcholine (ACh) release, as well as in single-channel recordings in cultured embryonic muscle. These data suggest that nAChRs desensitize faster in nra-2 mutants. Cell-surface expression of different subunits of the 'levamisole-sensitive' nAChR (L-AChR) is differentially affected in the absence of NRA-2 or NRA-4, suggesting that they control nAChR subunit composition or allow only certain receptor assemblies to leave the ER. The EMBO Journal (2009) 28, 2636-2649. doi: 10.1038/emboj.2009.204; Published online 16 July 2009 Subject Categories: membranes & transport; neuroscience