Article
- The EMBO Journal (2004) 23, 4156 - 4165
- doi:10.1038/sj.emboj.7600436
Published online: 14 October 2004
Subject Categories:
Regulation of nicotinic receptor expression by the ubiquitin–proteasome system
John C Christiansona and William N Green
- Department of Neurobiology, Pharmacology and Physiology, University of Chicago, Chicago, IL, USA
Correspondence to:
William N Green, Department of Neurobiology, Pharmacology and Physiology, University of Chicago, Chicago, IL 60637, USA. Tel.: +1 773 702 1763; Fax: +1 773 702 3774; E-mail: wgreen@midway.uchicago.edu
aPresent address: Department of Biological Sciences, Stanford University, Stanford, CA 94305-5430, USA
Received 8 March 2004; Accepted 14 September 2004
Abstract
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.
Keywords:
- acetylcholine receptor,
- endoplasmic reticulum-associated degradation,
- ubiquitin–proteasome system
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