QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, September 26, 2007, 27(39):10508-10519; doi:10.1523/JNEUROSCI.3353-07.2007

This Article Full Text Full Text (PDF) Supplemental Data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Rezvani, K. Articles by De Biasi, M. Search for Related Content PubMed PubMed Citation Articles by Rezvani, K. Articles by De Biasi, M. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB NICOTINE NICOTINE TARTRATE

 Previous Article  |  Next Article 

Cellular/Molecular
Nicotine Regulates Multiple Synaptic Proteins by Inhibiting Proteasomal Activity

Khosrow Rezvani,¹ Yanfen Teng,¹ David Shim,¹ and Mariella De Biasi^1,2,3

Departments of ¹Neuroscience and ²Molecular Physiology and Biophysics and ³Graduate Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, Texas 77030

Correspondence should be addressed to Mariella De Biasi, Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030. Email: debiasi{at}bcm.tmc.edu

Ubiquitination regulates the degradation, membrane trafficking, and transcription of proteins. At mammalian synapses, the ubiquitin–proteasome system (UPS) influences synaptic transmission and plasticity. Nicotine also has the ability to affect synaptic function via mechanisms that remain partially unknown. We found that nicotine, at concentrations achieved by smokers, reduced proteasomal activity, produced accumulation of ubiquitinated synaptic proteins, and increased total protein levels. In particular, a 24 h exposure to nicotine decreased proteasome-dependent degradation of the 7 nicotinic acetylcholine receptor (nAChR) subunit, as indicated by the accumulation of ubiquitinated 7. The same nicotine treatment increased the levels of the AMPA glutamate receptor subunit GluR1, the NMDA receptor subunit NR2A, the metabotropic receptor mGluR1, the plasticity factor Homer-1A, and the scaffolding postsynaptic density protein PSD-95, whereas the levels of another scaffolding protein, Shank, were reduced. These changes were associated with an inhibition of proteasomal chymotrypsin-like activity by nicotine. The nAChR antagonist mecamylamine was only partially able to block the effects of nicotine on the UPS, indicating that nAChR activation does not completely explain nicotine-induced inhibition of proteasomal catalytic activity. A competition binding assay suggested a direct interaction between nicotine and the 20S proteasome. These results suggest that the UPS might participate in nicotine-dependent synaptic plasticity.

Key words: nicotine; nicotinic acetylcholine receptor; proteasome; ubiquitin; glutamate receptors; mecamylamine

---

Received Jan. 29, 2007; revised Aug. 13, 2007; accepted Aug. 13, 2007.

Correspondence should be addressed to Mariella De Biasi, Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030. Email: debiasi{at}bcm.tmc.edu

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help