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Nicotinic receptor-lynx interactions

Institution: California Institute of Technology
Investigator(s): Julie Miwa, Ph.D.
Award Cycle: 2010 (Cycle 19) Grant #: 19KT-0032 Award: $278,797
Subject Area: Nicotine Dependence
Award Type: New Investigator Awards
Abstracts

Initial Award Abstract
The relevance of this proposal to the TRDRP's mission involves the understanding of factors underlying nicotine dependence. Activation of nicotinic acetylcholine receptors, the cognate receptors which bind nicotine, over time can promote long-term changes in the brain that lead to nicotine addiction. My colleagues and I have discovered a set of proteins, lynx molecules, which blunt the efficacy of nicotine - by binding to nicotinic acetylcholine receptors and dialing down receptor activity. Further, lynx molecules can counteract some of the long-term changes in the brain of the sort underlying nicotine addiction. In this way, lynx molecules exhibit features one would want in a smoking cessation compound - blunting the pleasurable aspects of nicotine and opposing the long-term changes in smoker's brains. This proposal addresses the mechanism by which lynx is able to achieve its effect in dialing down the activity of nicotinic receptors. A better understanding of lynx-receptor interactions is a promising direction for studying nicotine addiction and for developing smoking cessation strategies.
Publications

Nicotine remodels the endoplasmic reticulum through the Atf dependent pathway
Periodical: Molecular Pharmacology Index Medicus:
Authors: Srinivasan, R, Richards, CI, Mackey, EDW+, Rhee, DS+, Desphande, P, Miwa, JM and Lester, H ART
Yr: 2012 Vol: Nbr: Abs: Pg: PMID 22379121

Psychiatric drugs bind to their classical targets within the_x000d_ early exocytotic pathway
Periodical: Biological Psychiatry Index Medicus:
Authors: Lester, HA, Miwa, JM, and Srinivasan, R ART
Yr: Vol: Nbr: Abs: Pg:

Lynx1 balances neuronal activity_x000d_ through nicotinic acetylcholine receptor modulation. Biochem
Periodical: Biochemical Pharmacology Index Medicus:
Authors: Parker, RL+, Rhee, DS+, Mackey, EDW+, Lester, HA, and Miwa, JM ABS
Yr: 2011 Vol: 82 Nbr: 8 Abs: 2.6 Pg: 1037