Abstract
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 α3, β2, and β4 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 α3 and the two β 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 α7 nAChR subunit is a target of the UPS, point to a prominent role of the proteasome in nAChR trafficking.
Original language | English (US) |
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Pages (from-to) | 177-184 |
Number of pages | 8 |
Journal | Journal of Molecular Neuroscience |
Volume | 40 |
Issue number | 1-2 |
DOIs | |
State | Published - Jan 2010 |
Externally published | Yes |
Keywords
- Lysosome
- Nicotinic acetylcholine receptor
- Proteasome
- Protein trafficking
- Ubiquitin
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience