RIC-3: a nicotinic acetylcholine receptor chaperone.
RIC-3 is a transmembrane protein which acts as a molecular chaperone of nicotinic acetylcholine receptors (nAChRs). For some nAChR subtypes (such as homomeric alpha7 neuronal nAChRs), RIC-3 is required for efficient receptor folding, assembly and functional expression. In contrast, for other nAChR subtypes (such as heteromeric alpha4beta2 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-HT(3)R). As with heteromeric nAChRs, apparently contradictory results have been reported for the influence of RIC-3 on 5-HT(3)R 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.
Millar
N S
NS
Department of Pharmacology, University College London, London, UK. n.millar@ucl.ac.uk
D000818:Animals; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D018832:Molecular Chaperones / Q000235:genetics / Q000502:physiology*; D010275:Parasympathetic Nervous System / Q000502:physiology; D011978:Receptors, Nicotinic / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D013347:Subcellular Fractions
D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; C496701:RIC3 protein, human; D011978:Receptors, Nicotinic