RIC-3 enhances functional expression of multiple nicotinic acetylcholine receptor subtypes in mammalian cells.

Article Details


Lansdell SJ, Gee VJ, Harkness PC, Doward AI, Baker ER, Gibb AJ, Millar NS

RIC-3 enhances functional expression of multiple nicotinic acetylcholine receptor subtypes in mammalian cells.

Mol Pharmacol. 2005 Nov;68(5):1431-8. Epub 2005 Aug 24.

PubMed ID
16120769 [ View in PubMed

Recent studies have shown that RIC-3, originally identified in Caenorhabditis elegans as the protein encoded by the gene resistance to inhibitors of cholinesterase (ric-3), can enhance functional expression of alpha7 nicotinic acetylcholine receptors (nAChRs). In the present study, the influence of C. elegans and human RIC-3 upon multiple homomeric (alpha7, alpha8, and alpha9) and heteromeric (alpha3beta2, alpha3beta4, alpha4beta2, alpha4beta4, and alpha9alpha10) nAChR subtypes has been examined in transfected mammalian cells by radioligand binding and functional characterization. Coexpression of RIC-3 facilitates a dramatic enhancement of the ability of alpha7 (and the closely related alpha8 subunit) to generate functional nAChRs in otherwise nonpermissive mammalian cells. In contrast, coexpression of RIC-3 did not facilitate functional expression of either homomeric alpha9 or heteromeric alpha9alpha10 nAChRs in mammalian cell lines. It is noteworthy that whereas RIC-3 has been reported to cause a marked functional inhibition of heteromeric nAChRs such as alpha3beta4 and alpha4beta2 expressed in Xenopus laevis oocytes, RIC-3 significantly enhances levels of functional expression of these and other (alpha3beta2 and alpha4beta4) heteromeric nAChRs when expressed in mammalian cell lines. In addition, the interaction of multiple nAChR subunits (alpha3, alpha4, alpha7, beta2, and beta4) with RIC-3 has been demonstrated by coimmunoprecipitation from metabolically labeled transfected cells. It is significant that coimmunoprecipitation experiments have provided evidence that RIC-3 associates with unassembled nAChR subunits, a finding that is consistent with previous suggestions that RIC-3 may act by enhancing the maturation (subunit folding and assembly) of nAChRs. We conclude that RIC-3 is an nAChR-associated protein that can enhance functional expression of multiple nAChR subtypes in transfected mammalian cells.

DrugBank Data that Cites this Article

NameUniProt ID
Neuronal acetylcholine receptor subunit alpha-4P43681Details
Neuronal acetylcholine receptor subunit beta-2P17787Details
Neuronal acetylcholine receptor subunit alpha-7P36544Details
Neuronal acetylcholine receptor subunit beta-4P30926Details
Neuronal acetylcholine receptor subunit alpha-3P32297Details
Protein RIC-3Q7Z5B4Details