The ubiquitin-proteasome system regulates the stability of neuronal nicotinic acetylcholine receptors

J Mol Neurosci. 2010 Jan;40(1-2):177-84. doi: 10.1007/s12031-009-9272-x. Epub 2009 Aug 20.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Boronic Acids / pharmacology
  • Bortezomib
  • Cell Compartmentation / physiology
  • Cell Membrane / metabolism
  • Endoplasmic Reticulum / metabolism
  • Enzyme Inhibitors / pharmacology
  • Golgi Apparatus / metabolism
  • Nerve Tissue Proteins / metabolism
  • Neurons / metabolism*
  • PC12 Cells
  • Proteasome Endopeptidase Complex / metabolism*
  • Proteasome Inhibitors
  • Protein Stability
  • Protein Subunits / metabolism
  • Protein Transport / physiology
  • Pyrazines / pharmacology
  • Rats
  • Receptors, Nicotinic / metabolism*
  • Ubiquitin / metabolism*
  • Ubiquitination / drug effects
  • Ubiquitination / physiology*
  • Up-Regulation / physiology


  • Boronic Acids
  • Chrnb4 protein, mouse
  • Enzyme Inhibitors
  • Nerve Tissue Proteins
  • Proteasome Inhibitors
  • Protein Subunits
  • Pyrazines
  • Receptors, Nicotinic
  • Ubiquitin
  • nicotinic receptor beta2
  • nicotinic receptor subunit alpha3
  • Bortezomib
  • Proteasome Endopeptidase Complex