The ubiquitin-proteasome system regulates the stability of neuronal nicotinic acetylcholine receptors.
Ubiquitination is a key event for protein degradation by the proteasome system, membrane protein internalization, and protein trafficking among cellular compartments. Few data are available on the role of the ubiquitin-proteasome system (UPS) in the trafficking of neuronal nicotinic acetylcholine receptors (nAChRs). Experiments conducted in neuron-like differentiated rat pheochromocytoma cells (PC12 cells) show that the alpha3, beta2, and beta4 nAChR subunits are ubiquitinated and that their ubiquitination is necessary for degradation. A 24-h treatment with the proteasome inhibitor PS-341 increased the total levels of alpha3 and the two beta subunits in both whole cell lysates and fractions enriched for the ER/Golgi compartment. nAChR subunit upregulation was also detected in plasma membrane-enriched fractions. Inhibition of the lysosomal degradation machinery by E-64 had a significantly smaller effect on nAChR turnover. The present data, together with previous results showing that the alpha7 nAChR subunit is a target of the UPS, point to a prominent role of the proteasome in nAChR trafficking.
Rezvani
Khosrow
K
Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.
Teng
Yanfen
Y
De Biasi
Mariella
M
D000818:Animals; D001897:Boronic Acids / Q000494:pharmacology; D000069286:Bortezomib; D002451:Cell Compartmentation / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006056:Golgi Apparatus / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D016716:PC12 Cells; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors; D055550:Protein Stability; D021122:Protein Subunits / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D011719:Pyrazines / Q000494:pharmacology; D051381:Rats; D011978:Receptors, Nicotinic / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*; D054875:Ubiquitination / Q000187:drug effects / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology
D001897:Boronic Acids; D000069286:Bortezomib; D004791:Enzyme Inhibitors; D009419:Nerve Tissue Proteins; D046988:Proteasome Endopeptidase Complex; D061988:Proteasome Inhibitors; D021122:Protein Subunits; D011719:Pyrazines; D011978:Receptors, Nicotinic; D025801:Ubiquitin; C486720:Chrnb4 protein, mouse
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