Proteins interacting with nicotinic acetylcholine receptors: expanding functional and therapeutic horizons

Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels that carry out the fast actions of the neurotransmitter acetylcholine (ACh). Over the past 30 years, it has become clear that the activity of nAChRs is dependent on their interaction with a host of proteins, and the number of these that have been identified has increased considerably with recent large-scale proteomic analyses. This review focuses on these interacting proteins, discussing how they regulate a wide range of functions including receptor assembly, and trafficking to and from the cell surface, as well as how they directly modulate functional characteristics such as sensitivity and the degree of response to ACh. Mutations giving rise to disease states highlight the importance of these interacting proteins. Here, we consider their potential as future therapeutic targets for treating diseases associated with altered nAChR function.