Regulation of nicotinic receptor expression by the ubiquitin-proteasome system

被引:88
作者
Christianson, JC [1 ]
Green, WN [1 ]
机构
[1] Univ Chicago, Dept Neurobiol Pharmacol & Physiol, Chicago, IL 60637 USA
关键词
acetylcholine receptor; endoplasmic reticulum-associated degradation; ubiquitin-proteasome system;
D O I
10.1038/sj.emboj.7600436
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:4156 / 4165
页数:10
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