Affinage

RIC3

Protein RIC-3 · UniProt Q7Z5B4

Length
369 aa
Mass
41.1 kDa
Annotated
2026-04-28
50 papers in source corpus 26 papers cited in narrative 26 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RIC3 is an endoplasmic reticulum-resident transmembrane chaperone that promotes the folding, assembly, and surface delivery of nicotinic acetylcholine receptors (nAChRs) and serotonin type-3 (5-HT3) receptors in a subtype-specific manner. It possesses a cleavable N-terminal signal sequence, a single-pass transmembrane topology with its N-terminus in the ER lumen and a cytoplasmic coiled-coil domain, and interacts transiently with unassembled receptor subunits—binding α7 nAChR subunits via its transmembrane domains and 5-HT3A subunits via a duplicated DWLR motif in the intracellular domain—to facilitate pentameric receptor maturation at low concentrations while causing ER retention at high concentrations (PMID:11867529, PMID:15504725, PMID:19812337, PMID:20668195, PMID:37026993). Its steady-state levels are controlled by BATH-42/CUL-3-mediated ubiquitin-dependent degradation, and casein kinase II phosphorylation at Ser-164 expands its regulatory scope to include GABAA receptors, enabling coordinated tuning of excitatory and inhibitory neurotransmission (PMID:19223395, PMID:27489343). RIC3 is functionally required for the cholinergic anti-inflammatory pathway in macrophages through its role in α7 nAChR maturation (PMID:27129882, PMID:32179243).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2002 High

    The fundamental question of whether a dedicated accessory factor exists for nAChR maturation was answered when ric-3 mutants in C. elegans showed selective loss of nAChR function with mislocalized receptor protein, and heterologous co-expression rescued α7 nAChR activity.

    Evidence Genetic mutant analysis in C. elegans combined with heterologous expression and electrophysiology in Xenopus oocytes

    PMID:11867529

    Open questions at the time
    • Mechanism of action (folding vs. trafficking vs. assembly) was unresolved
    • Mammalian relevance not yet established
    • No physical interaction demonstrated
  2. 2003 High

    Whether RIC-3 acts uniformly on all Cys-loop receptors or has subtype-specific effects was resolved: human RIC-3 enhances α7 nAChR but inhibits α4β2, α3β4 nAChRs and abolishes 5-HT3 receptor currents, establishing differential regulation across the receptor superfamily.

    Evidence Heterologous co-expression of human RIC-3 with multiple receptor subtypes in Xenopus oocytes with electrophysiology

    PMID:12821669

    Open questions at the time
    • Molecular basis of subtype selectivity unknown
    • Whether effects reflect folding, assembly, or trafficking was unresolved
  3. 2004 High

    The question of whether RIC-3 physically associates with its target receptors and at which biosynthetic step it acts was addressed: co-immunoprecipitation confirmed direct interaction with α7, and surface biotinylation showed α7 protein reaches the membrane without RIC-3 but lacks functional conformation, establishing RIC-3 as a folding/assembly factor rather than a trafficking escort.

    Evidence Co-immunoprecipitation, surface biotinylation, α-bungarotoxin binding, and patch clamp in HEK293 cells

    PMID:15504725

    Open questions at the time
    • Subcellular site of action not yet pinpointed
    • Whether RIC-3 acts on monomers vs. oligomeric intermediates unclear
  4. 2005 High

    Multiple studies converged to define RIC-3's subcellular locale, domain requirements, and breadth of receptor substrates: RIC-3 was localized to the ER as a transient interactor; its transmembrane domains were shown to mediate chaperone activity (coiled-coil dispensable for some substrates); and specific receptor determinants (α7 ICD amphipathic helix, 5-HT3A extracellular isoleucine) were identified as governing enhancement versus inhibition of surface expression.

    Evidence ER co-localization with BiP, co-IP time-course, domain deletion mutagenesis, chimeric receptor analysis in oocytes and mammalian cells

    PMID:15809299 PMID:15927954 PMID:15932871 PMID:16120769

    Open questions at the time
    • Membrane topology not yet determined
    • Mechanism by which TM domains mediate chaperone function unknown
    • Whether coiled-coil self-association contributes to function was unresolved
  5. 2007 High

    The role of the coiled-coil domain in RIC-3 aggregation and whether isoform diversity modulates function was clarified: the coiled-coil drives aggregation and ER retention, while a truncated isoform lacking it traffics to the Golgi yet retains chaperone activity for homomeric 5-HT3A receptors.

    Evidence Live-cell fluorescence microscopy with FRAP, isoform comparison, surface expression assays in mammalian cells

    PMID:17609200

    Open questions at the time
    • Whether coiled-coil-mediated aggregation is physiologically relevant or an overexpression artifact was unclear
    • In vivo isoform-specific functions not established
  6. 2009 High

    RIC-3's membrane topology and the functional significance of self-association were resolved: mouse RIC-3 is a type I single-pass TM protein with a cleavable signal sequence, an ER-lumenal N-terminus, and a cytoplasmic coiled-coil that mediates homotypic self-association required for efficient α7 assembly; separately, conserved TM2 residues were shown essential for receptor interactions, and RIC-3 was predicted to be intrinsically disordered, enabling conformational plasticity for different substrates.

    Evidence Signal sequence mutagenesis, topology analysis, co-IP of self-association and receptor interaction, TM2 mutagenesis in oocytes

    PMID:19812337 PMID:19899809

    Open questions at the time
    • No structural data for RIC-3 or RIC-3–receptor complexes
    • Intrinsic disorder prediction not experimentally validated
  7. 2009 High

    A mechanism controlling RIC-3 protein levels was identified: BATH-42 recruits RIC-3 to the CUL-3 ubiquitin ligase complex for proteasomal degradation, and loss of BATH-42 elevates RIC-3 and paradoxically decreases nAChR function, revealing that RIC-3 dosage is tightly regulated for optimal receptor maturation.

    Evidence Yeast two-hybrid, in vitro binding, C. elegans genetic epistasis with cul-3 and ric-3 mutants

    PMID:19223395

    Open questions at the time
    • Ubiquitination sites on RIC-3 not mapped
    • Whether this pathway operates in mammals unknown
  8. 2010 High

    The dose-dependent duality of RIC-3 function was established: at low levels it promotes α7 assembly and ER export, while at high levels it causes ER retention; in neurons, RIC-3 co-traffics with α7 in dendritic ER subcompartments, restricting receptor delivery to dendrites and preventing axonal transport.

    Evidence Quantitative live-cell imaging, α-bungarotoxin surface labeling, subcellular fractionation in PC12 cells and cultured neurons

    PMID:20668195

    Open questions at the time
    • Whether dendritic restriction is a physiological regulatory mechanism or an overexpression effect is unclear
    • In vivo neuronal validation lacking
  9. 2016 High

    RIC-3's functional scope was expanded beyond nAChRs to inhibitory receptors: casein kinase II phosphorylation at Ser-164 enables phospho-RIC-3 to inhibit GABAA receptor function in addition to modulating nAChRs, providing a single post-translational switch for coordinated excitation-inhibition balance.

    Evidence Phosphosite mutagenesis, genetic epistasis with kin-10 and tax-6, electrophysiology in C. elegans

    PMID:27489343

    Open questions at the time
    • Direct physical interaction between RIC-3 and GABAA receptors not demonstrated
    • Phosphorylation-dependent mechanism not characterized biochemically
    • Mammalian conservation of this regulation not tested
  10. 2016 Medium

    RIC-3 was placed in an immunological context: its expression in macrophages is regulated by inflammatory signals, and silencing RIC-3 abolishes the cholinergic anti-inflammatory response, establishing it as essential for α7 nAChR-dependent immune regulation; separately, disease-associated RIC3 mutations (P57T, V168L) act as dominant negatives reducing endogenous α7 membrane levels.

    Evidence siRNA knockdown in macrophages with cytokine readouts; transfection of mutant RIC3 in PC12 cells with membrane fractionation and confocal microscopy

    PMID:27055476 PMID:27129882

    Open questions at the time
    • In vivo immune phenotype of RIC3 knockout not tested
    • Whether dominant-negative variants cause disease in patients not established by genetic segregation
  11. 2023 Medium

    The precise receptor determinants for RIC-3 interaction were mapped: a duplicated DWLR motif in the 5-HT3A intracellular domain was identified as critical for RIC-3 binding and functional modulation, and specific nAChR residues (cys-loop R/K159 and C-terminal I504) were shown to determine whether a receptor requires RIC-3 for functional expression.

    Evidence Synthetic peptide binding and alanine scanning mutagenesis for 5-HT3A; chimeric receptor construction and point mutagenesis with electrophysiology for nAChRs

    PMID:37026993 PMID:37417463

    Open questions at the time
    • No co-crystal or cryo-EM structure of RIC-3–receptor complex
    • Whether these determinants operate identically in neuronal contexts unknown
  12. 2024 Medium

    A human RIC3 variant (G88R) associated with a cognitive phenotype was shown to increase RIC3–α7 ER interaction strength while decreasing surface delivery, consistent with a loss-of-function mechanism where excessive ER retention impairs receptor maturation.

    Evidence FRET microscopy, 125I-α-bungarotoxin surface binding, functional assays in mammalian cells

    PMID:38472514

    Open questions at the time
    • Genetic causality for the cognitive phenotype not established
    • Whether G88R affects other receptor substrates untested
    • No in vivo model of this variant

Open questions

Synthesis pass · forward-looking unresolved questions
  • No high-resolution structure of RIC-3 or a RIC-3–receptor complex exists, the mechanism by which RIC-3 transmembrane domains promote subunit folding is unknown, and the physiological functions of RIC-3 in the mammalian nervous system and immune system have not been characterized in knockout animal models.
  • No structural model of RIC-3 alone or in complex with any receptor
  • In vivo mammalian knockout phenotype unreported
  • Mechanism of intrinsic disorder in substrate selectivity uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0044183 protein folding chaperone 6 GO:0098772 molecular function regulator activity 3
Localization
GO:0005783 endoplasmic reticulum 4
Pathway
R-HSA-392499 Metabolism of proteins 4 R-HSA-168256 Immune System 2 R-HSA-9609507 Protein localization 2
Partners
BATH-42CHRNA3CHRNA4CHRNA7CHRNB2CHRNB4CUL3HTR3A

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 C. elegans RIC-3 is specifically required for maturation of nicotinic acetylcholine receptors (nAChRs) but not GABA or glutamate receptors expressed in the same cells; in ric-3 mutants the DEG-3 receptor accumulates in cell bodies instead of cell processes, and co-expression of ric-3 in Xenopus oocytes enhances DEG-3/DES-2 and rat α7 nAChR activity, establishing RIC-3 as a selective nAChR maturation factor. Genetic mutant analysis in C. elegans, receptor localization imaging, heterologous expression in Xenopus oocytes with electrophysiology The EMBO journal High 11867529
2003 Human RIC-3 (hRIC3), a member of a conserved gene family with two transmembrane domains and a coiled-coil domain, enhances C. elegans DEG-3/DES-2, rat α7, and human α7 nAChR currents in Xenopus oocytes, but reduces human α4β2 and α3β4 nAChR currents and abolishes 5-HT3 receptor currents, demonstrating subtype-specific differential effects on pentameric ligand-gated ion channels. Heterologous expression in Xenopus oocytes with whole-cell electrophysiology; sequence/domain conservation analysis The Journal of biological chemistry High 12821669
2004 RIC-3 physically co-associates with α7 nAChR protein (shown by co-immunoprecipitation) and promotes formation of functional, surface-expressed α7 receptors in HEK293 cells; surface biotin labeling showed α7 protein reaches the plasma membrane without RIC-3 but lacks α-bungarotoxin binding (functional conformation), indicating RIC-3 is necessary for proper folding and/or assembly rather than membrane trafficking per se. Co-immunoprecipitation, whole-cell patch clamp, surface biotinylation, α-bungarotoxin binding in HEK293 cells The Journal of biological chemistry High 15504725
2005 RIC-3 co-immunoprecipitates with unassembled nAChR subunits (α3, α4, α7, β2, β4), and in mammalian cells enhances functional expression of multiple homomeric (α7, α8) and heteromeric (α3β2, α3β4, α4β2, α4β4) nAChR subtypes, with the exception of α9 and α9α10; this is consistent with RIC-3 acting on early maturation steps (subunit folding and assembly) rather than only at the fully assembled receptor stage. Radioligand binding, electrophysiology in transfected mammalian cells, co-immunoprecipitation from metabolically labeled cells Molecular pharmacology High 16120769
2005 hRIC-3 inhibits receptor surface expression of α4β2 nAChRs and 5-HT3 receptors by blocking export of mature receptors to the cell membrane (acting as a trafficking barrier); enhancement of α7 surface expression involves both increasing the number of mature receptors and facilitating transport, and requires specific amino acids in an amphipathic helix in the large cytoplasmic domain of α7; a specific extracellular isoleucine near TM1 in 5-HT3 determines RIC-3-induced transport arrest. Chimeric receptor analysis, mutagenesis, trafficking assays in Xenopus oocytes and mammalian cells The Journal of biological chemistry High 15927954
2005 RIC-3 is localized to the endoplasmic reticulum (co-localizing with BiP/GRP78) and transiently interacts with 5-HT3A receptors (interaction lasting <4 h); RIC-3 is not detected at significant levels on the cell surface, suggesting it functions as an ER-resident chaperone that promotes folding, assembly, or transport of 5-HT3A receptors without accompanying them to the plasma membrane. Immunofluorescence co-localization with ER marker BiP, co-immunoprecipitation time-course, surface expression assays in mammalian cells The Journal of biological chemistry High 15809299
2005 The effects of C. elegans RIC-3 on DEG-3/DES-2 nAChR functional expression and receptor kinetic/agonist-affinity properties are mediated by the transmembrane domains and do not require the coiled-coil domains; RIC-3 affects the quantity of DEG-3 subunit-containing receptor, suggesting stabilization of receptors or receptor intermediates; RIC-3 appears to preferentially promote maturation of DEG-3-rich receptor stoichiometries. Domain deletion mutagenesis, heterologous expression in Xenopus oocytes with electrophysiology, subunit ratio manipulation The Journal of biological chemistry High 15932871
2007 Human RIC-3 isoform a (RIC-3a) localizes to the ER reticular network and is highly mobile; the large coiled-coil domain drives protein aggregation; RIC-3a enhances surface expression of homomeric 5-HT3A receptors but inhibits surface expression of heteromeric 5-HT3A/B receptors; truncated isoform RIC-3d lacks the coiled-coil domain, localizes to ER and Golgi and cycles between them, does not aggregate, yet retains the ability to enhance homomeric and inhibit heteromeric 5-HT3 receptor surface expression. Live-cell fluorescence microscopy (GFP-tagged proteins), FRAP, surface expression assays, subcellular fractionation in mammalian cells The Journal of biological chemistry High 17609200
2007 Human RIC-3 protein is expressed in SH-SY5Y and PC12 neuronal cells, is induced upon differentiation, and is localized in rat brain regions where α7 nAChRs are found; in vitro translation demonstrated that the first TM domain of hRIC-3 mediates membrane insertion but does not act as a cleavable signal peptide; substitution of TM domains attenuates RIC-3 effects on nAChR expression; a specific linker length between TMs is required for α7 enhancement but not for α4β2 inhibition. In vitro translation, mutagenesis, immunohistochemistry in rat brain, immunoblot in differentiated neuronal cell lines Journal of neurochemistry Medium 18179477
2008 The conserved coiled-coil domain (CC-I) of C. elegans RIC-3 promotes maturation of specific nAChRs expressed in body-wall muscle in a receptor-specific manner in vivo; co-immunoprecipitation shows CC-I enhances RIC-3 interaction with nAChRs that require it; alternatively spliced RIC-3 isoforms lacking CC-I can still function for other nAChR subtypes, indicating redundancy with downstream sequences. In vivo genetic analysis in C. elegans, co-immunoprecipitation, heterologous expression in Xenopus oocytes Molecular biology of the cell High 19116311
2008 The nAChR chaperone activity of Drosophila RIC-3 does not require the coiled-coil domain (encoded by exon 7); inclusion of exon 2 (proline-rich N-terminal region) greatly reduces chaperone activity; host-cell specific factors modulate RIC-3 chaperone activity, as DmRIC-3 is more active than human RIC-3 in Drosophila cells and vice versa. Cloning of 11 alternatively spliced isoforms, heterologous co-expression in Drosophila and human cell lines, functional characterization Journal of neurochemistry Medium 18208544
2009 Mouse RIC-3 is targeted to the ER lumen by a cleavable N-terminal signal sequence (first 31 aa) and is a type I single-pass transmembrane protein with the N-terminus in the ER lumen and the coiled-coil domain in the cytoplasm; RIC-3 binds both unfolded and folded α7 subunits; the coiled-coil domain is not required for interaction with α7 but mediates homotypic RIC-3 self-association; facilitation of α7 surface expression requires the signal peptide, lumenal segment, and coiled-coil domain, suggesting self-association promotes efficient homomeric receptor assembly. Signal sequence deletion mutagenesis, topology analysis, co-immunoprecipitation, surface expression assays in mammalian cells The Journal of neuroscience High 19812337
2009 Conserved residues in the second RIC-3 transmembrane domain are required for interactions with DEG-3/DES-2 and ACR-16 nAChRs; additional domains beyond TM2 also contribute, with their relative importance differing between receptor types; differential subunit-specific interactions (RIC-3 increases surface DEG-3 but slightly reduces DES-2 surface expression) explain RIC-3 effects on receptor stoichiometry and properties; RIC-3 is predicted to be intrinsically disordered, potentially adopting different conformations with different receptors. Mutagenesis of conserved TM2 residues, heterologous co-expression in Xenopus oocytes, surface expression assays Biochemistry Medium 19899809
2009 BATH-42, a BTB-MATH domain protein, interacts with RIC-3 (demonstrated in yeast two-hybrid and in vitro), and also interacts with the CUL-3 ubiquitin ligase complex; loss of BATH-42 increases RIC-3 expression levels and decreases nAChR activity in C. elegans vulva muscles; overexpression of BATH-42 reduces nAChR function in a manner dependent on the RIC-3 C-terminus and CUL-3, indicating BATH-42 targets RIC-3 for CUL-3-mediated ubiquitin-proteasomal degradation to regulate RIC-3 levels. Yeast two-hybrid, in vitro interaction assay, C. elegans genetics, epistasis analysis, phenotypic assays (pharyngeal pumping) Journal of cell science High 19223395
2010 At low levels, Ric-3 promotes α7 nAChR assembly, ER release, and cell-surface delivery; at high levels, Ric-3 suppresses surface delivery and causes ER retention or aggregation without affecting assembly; in cultured neurons, Ric-3 and α7 subunits traffic together in rapidly moving vesicles to dendrites where Ric-3 is restricted to the ER subcompartment, confining α7 trafficking to dendrites and preventing axonal transport. Live-cell imaging, fluorescence microscopy, α-bungarotoxin surface labeling, subcellular fractionation in PC12 cells, cultured neurons, and transfected cells The Journal of neuroscience High 20668195
2010 RIC-3 directly interacts with 5-HT3A, -C, -D, and -E subunits (shown by co-localization in ER and co-immunoprecipitation) but exclusively enhances surface expression of homomeric 5-HT3A receptors; differential increases in surface Emax and Bmax indicate the effect is at the level of surface receptor number, not ligand affinity. Co-immunoprecipitation, immunocytochemistry, flow cytometry surface expression, radioligand binding, Ca2+ influx assay in HEK293 cells The Journal of biological chemistry High 20522555
2013 RIC-3 increases assembly and cell-surface trafficking of α7 receptors (measured by FRET between subunits and surface α-bungarotoxin binding) but does not alter total α7 protein expression; for α4β2 receptors, RIC-3 does not affect subunit assembly but increases α4 and β2 subunit protein levels; notably, co-expression of RIC-3 with α4β2 prevents nicotine-induced receptor upregulation, revealing a novel regulatory function. FRET microscopy with fluorescent protein-tagged subunits, α-bungarotoxin surface binding, immunoblot in HEK293T cells BMC neuroscience Medium 23586521
2016 Phosphorylation of C. elegans RIC-3 at Ser-164 by casein kinase II homologue KIN-10 (counteracted by calcineurin TAX-6) increases muscle excitability; phosphorylated RIC-3 inhibits GABAA receptor function in addition to its effects on nAChRs, providing coordinated dual regulation of excitation and inhibition; this represents a post-translational modification that expands RIC-3 function to inhibitory receptors. Phosphorylation site mutagenesis, C. elegans genetics, electrophysiology, epistasis with kinase/phosphatase mutants Molecular biology of the cell High 27489343
2019 The intracellular domain (ICD) of the 5-HT3A receptor is the site of interaction with RIC-3; a 24-amino-acid segment within the ICD (L1-MX segment) was identified as the minimal molecular determinant for RIC-3 binding using affinity pulldown assays with purified MBP-fused ICD deletion constructs. RIC-3 affinity pull-down assay with purified MBP-fused deletion constructs expressed in E. coli Biophysical journal Medium 31870537
2023 Two specific positions in the 5-HT3A ICD, W347/R349/L353 in the MX-helix and W447/R449/L454 at the MAM4-helix transition (duplicated DWLR motif), are critical for binding to RIC-3; alanine substitutions at these positions reduce RIC-3-mediated modulation of functional surface expression of the 5-HT3A receptor. Synthetic peptide binding assays, alanine scanning mutagenesis, functional surface expression assays in mammalian cells The Journal of general physiology Medium 37026993
2023 Two receptor residues (R/K at position 159 in the cys-loop and I at position 504 in the C-terminal tail of ACR-16) determine whether a nAChR requires RIC-3 for functional expression; chimeric and point mutation analysis showed that mutating these to E159 and T504 (residues found in RIC-3-dependent orthologs) confers a RIC-3 requirement on an otherwise RIC-3-independent receptor. Chimeric receptor construction, point mutagenesis, electrophysiology in Xenopus oocytes Protein science Medium 37417463
2024 A RIC3 variant G88R (associated with exceptional backwards speech/working memory) increases RIC3-α7 nAChR interactions in the ER (shown by FRET) and acts as a loss-of-function variant that decreases both cell-surface expression and functional expression of α7 nAChRs, compared to wild-type RIC3 which enhances both. FRET microscopy with fluorescent protein-tagged constructs, 125I-α-bungarotoxin surface binding, functional assays in mammalian cells Cellular and molecular life sciences Medium 38472514
2016 RIC-3 expression and splicing are regulated by inflammatory signals in immune cells; siRNA-mediated silencing of RIC-3 in a mouse macrophage cell line eliminates the anti-inflammatory effects of cholinergic agonists, placing RIC-3 upstream of the cholinergic anti-inflammatory pathway through its role in α7 nAChR functional expression. siRNA knockdown, electrophysiology in Xenopus oocytes, in situ hybridization, qRT-PCR, cytokine assays Molecular brain Medium 27129882
2020 siRNA-mediated silencing of RIC3 in a mouse macrophage cell line eliminates the anti-inflammatory effects of cholinergic agonists, confirming RIC3 is functionally required for the cholinergic anti-inflammatory pathway in immune cells, consistent with its role as α7 nAChR chaperone in these cells. siRNA knockdown in macrophage cell line, cytokine/inflammation assays International immunopharmacology Medium 32179243
2016 RIC3 mutations P57T and V168L act as dominant negatives in PC12 cells, reducing endogenous CHRNA7 (α7 nAChR) levels in membrane fractions and reducing co-localization of α7 with plasma membrane markers, demonstrating that RIC3 variants can alter functional receptor density at the cell surface. Transfection of mutant RIC3 in PC12 cells, Western blot of membrane fractions, confocal immunofluorescence co-localization Journal of medical genetics Medium 27055476
2026 RIC-3 directly interacts with the 5-HT3A intracellular domain (ICD) in native cellular contexts: a recombinant 5-HT3A ICD peptide specifically pulled down RIC-3 from plasma membrane fractions of Xenopus oocytes, ER fractions of SH-SY5Y cells, and mouse brain tissue; RIC-3 knockdown in SH-SY5Y cells reduced both ICD peptide binding and surface levels of α7 nAChR and 5-HT3A receptors. Peptide-resin pull-down from native cellular fractions (oocytes, neuronal cells, mouse brain), RIC-3 knockdown with surface receptor quantification bioRxivpreprint Medium 41756857

Source papers

Stage 0 corpus · 50 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 The C. elegans ric-3 gene is required for maturation of nicotinic acetylcholine receptors. The EMBO journal 202 11867529
2003 Conservation within the RIC-3 gene family. Effectors of mammalian nicotinic acetylcholine receptor expression. The Journal of biological chemistry 158 12821669
2004 Ric-3 promotes functional expression of the nicotinic acetylcholine receptor alpha7 subunit in mammalian cells. The Journal of biological chemistry 136 15504725
2005 RIC-3 enhances functional expression of multiple nicotinic acetylcholine receptor subtypes in mammalian cells. Molecular pharmacology 130 16120769
2008 RIC-3: a nicotinic acetylcholine receptor chaperone. British journal of pharmacology 104 18246096
2005 Dual role of the RIC-3 protein in trafficking of serotonin and nicotinic acetylcholine receptors. The Journal of biological chemistry 86 15927954
2005 Cell surface expression of 5-hydroxytryptamine type 3 receptors is promoted by RIC-3. The Journal of biological chemistry 60 15809299
2008 Host-cell specific effects of the nicotinic acetylcholine receptor chaperone RIC-3 revealed by a comparison of human and Drosophila RIC-3 homologues. Journal of neurochemistry 51 18208544
2010 Ric-3 promotes alpha7 nicotinic receptor assembly and trafficking through the ER subcompartment of dendrites. The Journal of neuroscience : the official journal of the Society for Neuroscience 43 20668195
2007 Differential subcellular localization of RIC-3 isoforms and their role in determining 5-HT3 receptor composition. The Journal of biological chemistry 41 17609200
2017 Role of the α7 Nicotinic Acetylcholine Receptor and RIC-3 in the Cholinergic Anti-inflammatory Pathway. Central nervous system agents in medicinal chemistry 40 27573666
2009 Mouse RIC-3, an endoplasmic reticulum chaperone, promotes assembly of the alpha7 acetylcholine receptor through a cytoplasmic coiled-coil domain. The Journal of neuroscience : the official journal of the Society for Neuroscience 38 19812337
2008 RIC-3 and nicotinic acetylcholine receptors: biogenesis, properties, and diversity. Biotechnology journal 38 18956371
2005 RIC-3 affects properties and quantity of nicotinic acetylcholine receptors via a mechanism that does not require the coiled-coil domains. The Journal of biological chemistry 36 15932871
2016 Evidence of mutations in RIC3 acetylcholine receptor chaperone as a novel cause of autosomal-dominant Parkinson's disease with non-motor phenotypes. Journal of medical genetics 32 27055476
2021 Neuroinflammation Modulation via α7 Nicotinic Acetylcholine Receptor and Its Chaperone, RIC-3. Molecules (Basel, Switzerland) 31 34684720
2010 RIC-3 exclusively enhances the surface expression of human homomeric 5-hydroxytryptamine type 3A (5-HT3A) receptors despite direct interactions with 5-HT3A, -C, -D, and -E subunits. The Journal of biological chemistry 29 20522555
2008 Functional properties of alpha7 nicotinic acetylcholine receptors co-expressed with RIC-3 in a stable recombinant CHO-K1 cell line. Assay and drug development technologies 29 18471073
2013 RIC-3 differentially modulates α4β2 and α7 nicotinic receptor assembly, expression, and nicotine-induced receptor upregulation. BMC neuroscience 28 23586521
2013 Chemical chaperones exceed the chaperone effects of RIC-3 in promoting assembly of functional α7 AChRs. PloS one 26 23638015
2007 Molecular characterization and localization of the RIC-3 protein, an effector of nicotinic acetylcholine receptor expression. Journal of neurochemistry 26 18179477
2016 RIC-3 expression and splicing regulate nAChR functional expression. Molecular brain 21 27129882
2013 Cell-specific effects on surface α7 nicotinic receptor expression revealed by over-expression and knockdown of rat RIC3 protein. Journal of neurochemistry 20 23157401
2007 Lack of RIC-3 congruence with beta2 subunit-containing nicotinic acetylcholine receptors in bipolar disorder. Neuroscience 20 17640815
2006 Role of the RIC-3 protein in trafficking of serotonin and nicotinic acetylcholine receptors. Journal of molecular neuroscience : MN 20 17192664
2012 Xenopus laevis RIC-3 enhances the functional expression of the C. elegans homomeric nicotinic receptor, ACR-16, in Xenopus oocytes. Journal of neurochemistry 17 22970690
2009 Receptor and subunit specific interactions of RIC-3 with nicotinic acetylcholine receptors. Biochemistry 17 19899809
2008 The conserved RIC-3 coiled-coil domain mediates receptor-specific interactions with nicotinic acetylcholine receptors. Molecular biology of the cell 17 19116311
2009 The BTB-MATH protein BATH-42 interacts with RIC-3 to regulate maturation of nicotinic acetylcholine receptors. Journal of cell science 16 19223395
2009 Ric-3 chaperone-mediated stable cell-surface expression of the neuronal alpha7 nicotinic acetylcholine receptor in mammalian cells. Acta pharmacologica Sinica 15 19498422
2020 Why Does Knocking Out NACHO, But Not RIC3, Completely Block Expression of α7 Nicotinic Receptors in Mouse Brain? Biomolecules 14 32204458
2020 RIC3, the cholinergic anti-inflammatory pathway, and neuroinflammation. International immunopharmacology 13 32179243
2022 Speculation on How RIC-3 and Other Chaperones Facilitate α7 Nicotinic Receptor Folding and Assembly. Molecules (Basel, Switzerland) 10 35889400
2019 Delineating the Site of Interaction of the 5-HT3A Receptor with the Chaperone Protein RIC-3. Biophysical journal 10 31870537
2016 RIC-3 phosphorylation enables dual regulation of excitation and inhibition of Caenorhabditis elegans muscle. Molecular biology of the cell 10 27489343
2008 Molecular cloning and characterization of a novel human variant of RIC-3, a putative chaperone of nicotinic acetylcholine receptors. Bioscience reports 10 18691158
2015 Resistance to Inhibitors of Cholinesterase 3 (Ric-3) Expression Promotes Selective Protein Associations with the Human α7-Nicotinic Acetylcholine Receptor Interactome. PloS one 9 26258666
2022 Effects of cofactors RIC-3, TMX3 and UNC-50, together with distinct subunit ratios on the agonist actions of imidacloprid on Drosophila melanogaster Dα1/Dβ1 nicotinic acetylcholine receptors expressed in Xenopus laevis oocytes. Pesticide biochemistry and physiology 8 36127041
2024 Impact of a worker bee thoracic ganglion RIC-3 variant on the actions of acetylcholine and neonicotinoids on nicotinic receptors in Apis mellifera. Pest management science 5 39167025
2017 RIC3 variants are not associated with Parkinson's disease in French-Canadians and French. Neurobiology of aging 5 28153381
2023 Two residues determine nicotinic acetylcholine receptor requirement for RIC-3. Protein science : a publication of the Protein Society 4 37417463
2017 Dual effects of insect nAChR chaperone RIC-3 on hybrid receptor: Promoting assembly on endoplasmic reticulum but suppressing transport to plasma membrane on Xenopus oocytes. Neurochemistry international 4 29032010
2024 N-Glycosylation Deficiency in Transgene α7 nAChR and RIC3 Expressing CHO Cells Without NACHO. The Journal of membrane biology 3 38967800
2017 Genetic analysis of the RIC3 gene in Han Chinese patients with Parkinson's disease. Neuroscience letters 3 28606768
2024 Unraveling the molecular interactions between α7 nicotinic receptor and a RIC3 variant associated with backward speech. Cellular and molecular life sciences : CMLS 2 38472514
2023 Deletion induced splicing in RIC3 drives nicotinic acetylcholine receptor regulation with implications for endoplasmic reticulum stress in human astrocytes. Glia 2 36602087
2025 Effects of Swapping 5HT3 and α7 Residues in Chimeric Receptor Proteins on RIC3 and NACHO Chaperone Actions. Molecules (Basel, Switzerland) 1 41226195
2023 Binding motif for RIC-3 chaperon protein in serotonin type 3A receptors. The Journal of general physiology 1 37026993
2012 Relationship of RIC-3 gene rs1528133 polymorphism with varying degrees of body weight and eating behavior. Diabetes & metabolic syndrome 1 23153976
2026 RIC-3 Interacts Directly with the 5-HT3A Receptor to Mediate Trafficking Across Subcellular Compartments. bioRxiv : the preprint server for biology 0 41756857