Regulation of nicotinic receptor expression by the ubiquitin-proteasome system.
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.
Department of Neurobiology, Pharmacology and Physiology, University of Chicago, Chicago, IL 60637, USA.
John C
JC
Christianson
William N
WN
Green
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D002038:Bungarotoxins / Q000378:metabolism; D002460:Cell Line; D015853:Cysteine Proteinase Inhibitors / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors; D021122:Protein Subunits / Q000378:metabolism*; D021381:Protein Transport; D011869:Radioligand Assay; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*
D002038:Bungarotoxins; D015853:Cysteine Proteinase Inhibitors; D061988:Proteasome Inhibitors; D021122:Protein Subunits; D011978:Receptors, Nicotinic; D025801:Ubiquitin; C067713:lactacystin; D046988:Proteasome Endopeptidase Complex; D000111:Acetylcysteine