Regulation of nicotinic receptor expression by the ubiquitin-proteasome system
Regulation of nicotinic receptor expression by the ubiquitin-proteasome system
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DOI：
10.1038/sj.emboj.7600436
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发表时间：
2004-10-27
期刊：
影响因子：
11.4
通讯作者：
Green, WN
中科院分区：
文献类型：
--
作者：
Christianson, JC;Green, WN
配体门控离子通道（LGIC）表达的调控对突触的形成、维持和可塑性至关重要。用蛋白酶体抑制剂处理小鼠肌管增加了表面烟碱乙酰胆碱受体（AChR）的数量，表明LGIC表达受泛素-蛋白酶体系统（UPS）调节。升高的表面表达导致增加AChR传递到质膜，而不是从减少营业额的表面。AChR运输的增加是内质网（ER）中亚基组装增加的直接结果。由于蛋白酶体抑制剂也阻断了未组装AChR亚基的ER相关降解（ERAD），因此数据表明，额外的AChR是由通常针对ERAD的亚基组装而成的。我们的数据表明，AChR表面表达的UPS通过ERAD，其活性决定寡聚体受体组装效率的调节。
Control of ligand-gated ion channel (LGIC) expression is essential for the formation, maintenance and plasticity of synapses. Treatment of mouse myotubes with proteasome inhibitors increased the number of surface nicotinic acetylcholine receptors (AChRs), indicating LGIC expression is regulated by the ubiquitin - proteasome system ( UPS). Elevated surface expression resulted from increased AChR delivery to the plasma membrane and not from decreased turnover from the surface. The rise in AChR trafficking was the direct result of increased assembly of subunits in the endoplasmic reticulum ( ER). Because proteasome inhibitors also blocked ER-associated degradation (ERAD) of unassembled AChR subunits, the data indicate that the additional AChRs were assembled from subunits normally targeted for ERAD. Our data show that AChR surface expression is regulated by the UPS through ERAD, whose activity determines oligomeric receptor assembly efficiency.