| First Author | Fox AM | Year | 2015 |
| Journal | J Biol Chem | Volume | 290 |
| Issue | 40 | Pages | 24403-12 |
| PubMed ID | 26269589 | Mgi Jnum | J:225867 |
| Mgi Id | MGI:5694854 | Doi | 10.1074/jbc.M115.661827 |
| Citation | Fox AM, et al. (2015) The Nicotine Metabolite, Cotinine, Alters the Assembly and Trafficking of a Subset of Nicotinic Acetylcholine Receptors. J Biol Chem 290(40):24403-12 |
| abstractText | Exposure to nicotine alters the trafficking and assembly of nicotinic receptors (nAChRs), leading to their up-regulation on the plasma membrane. Although the mechanism is not fully understood, nicotine-induced up-regulation is believed to contribute to nicotine addiction. The effect of cotinine, the primary metabolite of nicotine, on nAChR trafficking and assembly has not been extensively investigated. We utilize a pH-sensitive variant of GFP, super ecliptic pHluorin, to differentiate between intracellular nAChRs and those expressed on the plasma membrane to quantify changes resulting from cotinine and nicotine exposure. Similar to nicotine, exposure to cotinine increases the number of alpha4beta2 receptors on the plasma membrane and causes a redistribution of intracellular receptors. In contrast to this, cotinine exposure down-regulates alpha6beta2beta3 receptors. We also used single molecule fluorescence studies to show that cotinine and nicotine both alter the assembly of alpha4beta2 receptors to favor the high sensitivity (alpha4)2(beta2)3 stoichiometry. |
