Home Write to the Editor
Biochemistry news, hot off the press Society news, hot off the press Conferences, meetings, seminars, courses Jobs Grants, awards Read or write one! Current edition of The Biochemist

2 January 2014

Nicotine exploits COPI to foster addiction

A study helps explain how nicotine exploits the body’s cellular machinery to promote addiction.

The findings in The Journal of General Physiology could lead to new therapies to help people quit smoking.

According to the Center for Disease Control and Prevention, tobacco accounts for the greatest number of preventable deaths worldwide by any single agent. Nicotine, the active ingredient of tobacco, activates receptors known as nAChRs and, remarkably, unlike most other drugs of abuse, it acts as a ‘pharmacological chaperone’ to stabilize assembly of its receptors within the Endoplasmic Reticulum (ER) and increase their abundance at the cell surface (up-regulation). Up-regulation of nAChRs plays a major role in nicotine addiction and, possibly, in the decreased susceptibility of smokers to Parkinson’s disease.

Receptors containing an α6 subunit (α6* nAChRs) are abundant in several specific brain regions. Researchers from the California Institute of Technology in Pasadena used mice expressing α6 labelled with a fluorescent protein to show that exposure to nicotine—at a level comparable to that in human smokers—up-regulated α6* nAChRs in these areas of the brain.

Unexpectedly, the researchers discovered that nicotine’s ability to up-regulate α6* nAChRs relied on the retrograde transport of α6* nAChRs back from the Golgi to the ER by COPI-coated vesicles. The authors believe that Golgi–ER cycling (involving COPI vesicles) may be a common mechanism for up-regulation of other nAChRs by nicotine. Manipulation of this process could therefore help form new strategies for smoking cessation and neuroprotection against Parkinson’s disease.



 
Biochemical Society Homepage More top news stories
Bristol team creates designer ‘barrel’ proteins
Some scientists share better than others
Tarantula venom illuminates electrical activity in live cells