Cell surface expression of 5-hydroxytryptamine type 3 receptors is promoted by RIC-3.
RIC-3 has been identified as a molecule essential for the recruitment of functional nicotinic acetylcholine receptors composed of alpha7, but it exhibits inhibitory effects on alpha4beta2 or alpha3beta4 receptors. In this study, we investigated the role of RIC-3 in the recruitment of 5-hydroxytryptamine type 3A (5-HT(3A)) receptors to the cell surface. Although RIC-3 is not essential for the surface transport of 5-HT(3A) receptors, we found that its presence enhances both receptor transport and function in a concentration-dependent manner. RIC-3 is localized to the endoplasmic reticulum, as evidenced by co-localization with the chaperone molecule, binding protein (BiP). RIC-3 is not detected at significant levels on the cell surface when expressed alone or in the presence of 5-HT(3A). RIC-3 and 5-HT(3A) show a low level interaction that is transient (<4 h). That RIC-3 can interact with an endoplasmic reticulum-retained 5-HT(3A) construct, combined with the transient interaction observed and lack of significant surface-expressed RIC-3, suggests that RIC-3 may play a role in 5-HT(3A) receptor folding, assembly, or transport to the cell surface.
Cheng
Aixin
A
Department of Pharmacology & Neuroscience, Ninewells Medical School, University of Dundee, Dundee DD1 9SY, Scotland, United Kingdom.
McDonald
Neil A
NA
Connolly
Christopher N
CN
D000818:Animals; D019921:Biotinylation; D019556:COS Cells; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins; D008564:Membrane Potentials; D008856:Microscopy, Fluorescence; D011485:Protein Binding; D017510:Protein Folding; D021381:Protein Transport; D011506:Proteins / Q000378:metabolism*; D044406:Receptors, Serotonin, 5-HT3 / Q000096:biosynthesis*; D013997:Time Factors
D018076:DNA, Complementary; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; C496701:RIC3 protein, human; D044406:Receptors, Serotonin, 5-HT3