RIC‐3: a nicotinic acetylcholine receptor chaperone

• Published in: British journal of pharmacology 2008-03, Vol.153 (S1), p.S177-S183
• Main Author: Millar, N S
• Format: Article
• Language: English
• Subjects: acetylcholine receptor; Acetylcholine receptors (nicotinic); Animals; Caenorhabditis elegans; Chaperones; Cholinesterase; Humans; Internet; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - physiology; Membrane proteins; molecular chaperone; Molecular Chaperones - genetics; Molecular Chaperones - physiology; Nematoda; nicotinic receptor; Parasympathetic Nervous System - physiology; Pharmacology; Receptors, Nicotinic - genetics; Receptors, Nicotinic - physiology; Review; RIC‐3; Serotonin; Serotonin S3 receptors; Signal Transduction; Subcellular Fractions
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0707661

RIC‐3 is a transmembrane protein which acts as a molecular chaperone of nicotinic acetylcholine receptors (nAChRs). For some nAChR subtypes (such as homomeric α7 neuronal nAChRs), RIC‐3 is required for efficient receptor folding, assembly and functional expression. In contrast, for other nAChR subtypes (such as heteromeric α4β2 neuronal nAChRs) there have been reports that RIC‐3 can both enhance and reduce levels of functional expression. There is also evidence that RIC‐3 can modulate maturation of the closely related 5‐hydroxytryptamine (5‐HT) receptor (5‐HT3R). As with heteromeric nAChRs, apparently contradictory results have been reported for the influence of RIC‐3 on 5‐HT3R maturation in different expression systems. Recent evidence indicates that these differences in RIC‐3 chaperone activity may be influenced by the host cell, suggesting that other proteins may play an important role in modulating the effects of RIC‐3 as a chaperone. RIC‐3 was originally identified in the nematode Caenorhabditis elegans as the protein encoded by the gene ric‐3 (resistance to inhibitors of cholinesterase) and has subsequently been cloned and characterized from mammalian and insect species. This review provides a brief history of RIC‐3; from the identification of the ric‐3 gene in C. elegans in 1995 to the more recent demonstration of its activity as a nAChR chaperone. British Journal of Pharmacology (2008) 153, S177–S183; doi:10.1038/sj.bjp.0707661; published online 4 February 2008