Affinage

RIC3

Protein RIC-3 · UniProt Q7Z5B4

Length
369 aa
Mass
41.1 kDa
Annotated
2026-06-10
50 papers in source corpus 25 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RIC-3 is an endoplasmic reticulum-resident transmembrane chaperone that controls the folding, assembly, and surface delivery of pentameric ligand-gated ion channels, principally nicotinic acetylcholine receptors (nAChRs) and 5-HT3 receptors (PMID:11867529, PMID:12821669, PMID:15809299). Identified in C. elegans as specifically required for maturation of multiple nAChRs but not GABA or glutamate receptors (PMID:11867529), it acts subtype-selectively: it enhances functional expression of homomeric receptors such as α7, α8, and homomeric 5-HT3A, while inhibiting or retaining heteromeric subtypes including α4β2, α3β4, and 5-HT3A/B (PMID:12821669, PMID:16120769, PMID:17609200, PMID:20522555). Co-immunoprecipitation establishes that RIC-3 transiently and directly binds unassembled receptor subunits in the ER to promote proper folding and oligomeric assembly rather than acting only at later trafficking steps (PMID:15504725, PMID:16120769, PMID:15809299). Topologically it is a single-pass type I transmembrane protein with a cleavable N-terminal signal sequence placing its N-terminus in the ER lumen and its coiled-coil domain in the cytoplasm; the transmembrane domains mediate receptor binding, while coiled-coil-dependent self-association drives efficient α7 assembly (PMID:19812337, PMID:19899809). Receptor specificity is encoded on both partners: RIC-3 recognizes intracellular-domain motifs in 5-HT3A—a duplicated DWLR/VLDR sequence in the MX-helix and MA-helix/M4 transition (PMID:31870537, PMID:37026993)—and discrete receptor residues (e.g., in ACR-16) dictate the dependency on RIC-3 (PMID:37417463). RIC-3 chaperone activity is dose-dependent, switching from promoting surface delivery at low levels to ER retention and aggregation at high levels (PMID:20668195), and is further controlled by CUL-3/BATH-42-mediated ubiquitylation that sets RIC-3 protein levels (PMID:19223395) and by Ser-164 phosphorylation under calcineurin/casein kinase II control, which extends its influence to excitation-inhibition balance via GABAA receptors (PMID:27489343). Functionally, RIC-3 is required for α7 nAChR-mediated cholinergic anti-inflammatory signaling in macrophages (PMID:27129882), and RIC3 missense variants that impair α7 trafficking have been linked to Parkinson's disease and to an exceptional-backward-speech phenotype (PMID:27055476, PMID:38472514).

Mechanistic history

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

    Established RIC-3 as a dedicated maturation factor for nAChRs, answering whether a specific accessory protein governs nicotinic receptor biogenesis distinct from other ionotropic receptors.

    Evidence C. elegans ric-3 loss-of-function genetics, immunolocalization of DEG-3, and Xenopus oocyte co-expression electrophysiology

    PMID:11867529

    Open questions at the time
    • Did not define the molecular mechanism of action (folding vs trafficking)
    • Did not establish subcellular site of action
    • Mammalian receptor scope untested at this stage
  2. 2003 High

    Demonstrated that the human ortholog is subtype-selective, showing RIC-3 can enhance some channels (α7) while suppressing others (α4β2, α3β4, 5-HT3), establishing differential modulation as a core feature.

    Evidence Xenopus oocyte co-expression whole-cell recording across multiple receptor subtypes plus expression analysis

    PMID:12821669

    Open questions at the time
    • Mechanism of opposite effects on different subtypes unexplained
    • Domain requirements undefined
    • Oocyte results later found to differ from mammalian cells
  3. 2004 High

    Showed RIC-3 physically associates with α7 and is required for folding/assembly rather than mere trafficking, since α7 reaches the surface without RIC-3 but is not functional.

    Evidence Whole-cell patch clamp, surface biotinylation, α-bungarotoxin binding and co-immunoprecipitation in HEK293 cells

    PMID:15504725

    Open questions at the time
    • Did not identify the interacting domains
    • Stoichiometry and transience of binding unresolved
  4. 2005 High

    Localized RIC-3 to the ER and defined its action as transient binding to unassembled/ER-retained subunits, fixing the cellular site and timing of chaperone activity; also mapped which receptor and RIC-3 regions drive enhancement vs transport arrest.

    Evidence BiP co-localization, co-IP time courses, chimeric receptor and site-directed mutagenesis, and domain analyses in mammalian cells and oocytes

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

    Open questions at the time
    • Precise binding motifs not yet defined
    • Membrane topology not established
    • Discrepancy between oocyte and mammalian heteromer effects unexplained
  5. 2009 High

    Resolved RIC-3 membrane topology and the division of labor among its domains, establishing that TM domains mediate receptor binding while the coiled-coil drives self-association required for efficient α7 assembly.

    Evidence Signal-sequence and protease-protection topology assays, deletion/domain mutagenesis, and co-IP distinguishing folded vs unfolded α7 binding in mammalian cells

    PMID:19116311 PMID:19812337 PMID:19899809

    Open questions at the time
    • Conformational basis for binding diverse receptors not structurally defined
    • Self-association stoichiometry unknown
  6. 2009 High

    Identified post-translational control of RIC-3 abundance, showing BATH-42 links RIC-3 to CUL-3-mediated ubiquitylation and degradation to tune chaperone levels.

    Evidence Yeast two-hybrid, in vitro interaction, and C. elegans genetic epistasis with electrophysiology

    PMID:19223395

    Open questions at the time
    • Ubiquitylation sites on RIC-3 not mapped
    • Conservation of this regulation in mammals untested
  7. 2010 High

    Demonstrated that RIC-3 effects are concentration-dependent, switching from promoting surface delivery at low levels to ER retention/aggregation at high levels, reconciling its dual enhancing/inhibitory behavior.

    Evidence Live imaging and co-trafficking in PC12 cells and neurons with surface α-bungarotoxin binding

    PMID:20668195

    Open questions at the time
    • Physiological control of RIC-3 dosage in vivo unclear
    • Relationship of aggregation to dendritic targeting mechanistically incomplete
  8. 2016 Medium

    Extended RIC-3 regulation to phosphorylation, showing Ser-164 phosphorylation under calcineurin/CKII control modulates excitability and broadens its influence to GABAA receptors.

    Evidence C. elegans in vivo phosphorylation analysis and genetic epistasis with electrophysiology

    PMID:27489343

    Open questions at the time
    • Direct phosphorylation of RIC-3 by these kinases not biochemically shown
    • Mammalian conservation of Ser-164 regulation untested
  9. 2016 Medium

    Linked RIC-3 to physiological cholinergic signaling beyond neurons, establishing it as required for α7 nAChR-mediated anti-inflammatory responses in immune cells.

    Evidence siRNA knockdown in macrophages with cholinergic anti-inflammatory functional readout plus expression/splicing analysis

    PMID:27129882

    Open questions at the time
    • Mechanism of inflammatory regulation of RIC3 splicing unresolved
    • Single functional readout
  10. 2019 Medium

    Mapped the 5-HT3A determinant of RIC-3 binding to a discrete 24-residue intracellular-domain segment, moving receptor recognition from region-level to motif-level resolution.

    Evidence MBP-fused ICD deletion constructs in RIC-3 affinity pull-down with purified proteins

    PMID:31870537

    Open questions at the time
    • Performed with purified fragments rather than full-length receptor in cells
    • Single lab
  11. 2023 High

    Defined RIC-3 recognition on both partners at residue resolution: a duplicated DWLR/VLDR motif in the 5-HT3A ICD and specific ACR-16 residues that confer dependency on RIC-3.

    Evidence Ala-scanning of synthetic peptides and full-length receptors with functional surface assays; reciprocal chimeric/point mutagenesis with oocyte electrophysiology

    PMID:37026993 PMID:37417463

    Open questions at the time
    • Structure of the RIC-3–receptor complex not solved
    • Whether the same motifs govern nAChR binding broadly untested
  12. 2024 Medium

    Connected RIC3 sequence variation to human phenotypes, showing disease-associated variants impair α7 surface delivery through aberrant ER retention or dominant-negative trafficking defects.

    Evidence FRET, 125I-α-bungarotoxin binding, and functional assays of variant RIC3 in PC12/HEK cells

    PMID:27055476 PMID:38472514

    Open questions at the time
    • Causality in patients not established by family/rescue studies in the corpus
    • Single variants studied per phenotype

Open questions

Synthesis pass · forward-looking unresolved questions
  • How RIC-3 structurally accommodates and discriminates among diverse receptor subunits to produce opposite (enhancing vs retaining) outcomes remains unresolved.
  • No high-resolution structure of a RIC-3–receptor complex
  • Molecular basis for subtype-selective enhancement vs retention unexplained
  • Mammalian counterparts of BATH-42/CUL-3 and Ser-164 regulation not identified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0044183 protein folding chaperone 5 GO:0098772 molecular function regulator activity 3
Localization
GO:0005783 endoplasmic reticulum 4
Pathway
R-HSA-392499 Metabolism of proteins 4 R-HSA-112316 Neuronal System 3 R-HSA-9609507 Protein localization 3
Partners
ACR-16BATH-42CHRNA4CHRNA7CHRNB2CUL-3DEG-3HTR3A

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 C. elegans RIC-3 is specifically required for the maturation (folding/assembly and proper trafficking) of at least four 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 the cell body rather than cell processes. Co-expression of ric-3 in Xenopus oocytes enhances activity of DEG-3/DES-2 and rat α7 nAChRs, demonstrating functional conservation. Genetic loss-of-function (C. elegans ric-3 mutants), immunolocalization, Xenopus oocyte co-expression electrophysiology The EMBO journal High 11867529
2003 Human RIC-3 (hRIC-3) belongs to a conserved gene family (two transmembrane domains + coiled-coil domain) and differentially modulates human nAChRs: it enhances α7 nAChR currents but reduces α4β2 and α3β4 nAChR currents, and totally abolishes 5-HT3 receptor currents while barely affecting α1 glycine receptor currents in Xenopus oocytes. hRIC-3 produces multiple isoforms and is expressed in neurons and muscles. Xenopus oocyte co-expression with whole-cell current recording, RT-PCR/expression analysis The Journal of biological chemistry High 12821669
2004 RIC-3 promotes formation of functional α7 nAChRs in mammalian HEK293 cells, as shown by whole-cell patch clamp and surface α-bungarotoxin binding. α7 and RIC-3 proteins co-associate by co-immunoprecipitation. RIC-3 enables α-bungarotoxin surface labeling even though α7 protein reaches the plasma membrane without RIC-3, indicating RIC-3 is required for proper folding/assembly (not merely trafficking) of α7 receptors. Whole-cell patch clamp, surface biotinylation, α-bungarotoxin binding, co-immunoprecipitation in HEK293 cells The Journal of biological chemistry High 15504725
2005 RIC-3 enhances functional expression of multiple homomeric (α7, α8) nAChR subtypes in transfected mammalian cells. Unlike in Xenopus oocytes, RIC-3 also enhances heteromeric nAChRs (α3β2, α3β4, α4β2, α4β4) in mammalian cells. Co-immunoprecipitation demonstrates RIC-3 associates with unassembled nAChR subunits (α3, α4, α7, β2, β4), consistent with a role in promoting subunit folding and assembly. Radioligand binding, patch clamp electrophysiology, co-immunoprecipitation from metabolically labeled transfected mammalian cells Molecular pharmacology High 16120769
2005 hRIC-3 inhibits surface expression of α4β2 nAChRs and 5-HT3 receptors by blocking export of mature receptors to the cell membrane, whereas it enhances α7 nAChR expression by increasing the number of mature receptors and facilitating membrane transport. The N-terminal region (two TM segments) and C-terminal region are both required for these differential effects. A specific extracellular isoleucine near the first TM domain of 5-HT3/α4β2 receptors mediates the transport arrest induced by hRIC-3. Specific amino acids in the amphipathic helix of the large cytoplasmic domain of α7 are required for enhancement. Chimeric receptor co-expression, site-directed mutagenesis, co-immunoprecipitation, confocal microscopy in Xenopus oocytes and mammalian cells The Journal of biological chemistry High 15927954
2005 RIC-3 is localized to the endoplasmic reticulum (co-localization with BiP). RIC-3 enhances surface transport and function of 5-HT3A receptors in a concentration-dependent manner. The interaction between RIC-3 and 5-HT3A is transient (<4 h). RIC-3 can interact with an ER-retained 5-HT3A construct, suggesting a role in folding/assembly rather than later trafficking steps. RIC-3 is not detected at significant levels on the cell surface. Confocal co-localization with BiP (ER marker), co-immunoprecipitation time course, surface expression assays in mammalian cells The Journal of biological chemistry High 15809299
2005 RIC-3 effects on DEG-3/DES-2 nAChR functional expression and receptor kinetics/agonist affinity are mediated by the transmembrane domains and do not require the coiled-coil domains. RIC-3 preferentially promotes maturation of DEG-3-rich receptors, affecting the subunit composition of assembled receptors. RIC-3 also stabilizes receptor intermediates (affects DEG-3 quantity). Xenopus oocyte co-expression electrophysiology, deletion/domain-swap mutagenesis, receptor subunit ratio manipulation The Journal of biological chemistry High 15932871
2007 Human RIC-3 isoform a (RIC-3a) is targeted to the ER by an N-terminal signal sequence and forms diffuse reticular and halo structures; it is highly mobile within the ER. RIC-3a enhances surface expression of homomeric 5-HT3A receptors but inhibits surface expression of heteromeric 5-HT3A/B receptors. A truncated isoform (RIC-3d), lacking the large coiled-coil C-terminal domain, localizes to ER and cycles between ER and Golgi, does not aggregate, yet retains the ability to enhance homomeric and inhibit heteromeric 5-HT3 receptor surface expression. Fluorescence live imaging (FRAP), confocal co-localization, flow cytometry surface expression assays in mammalian cells The Journal of biological chemistry High 17609200
2007 hRIC-3 membrane topology: in vitro translation showed membrane insertion but the first TM domain does not act as a signal peptide. Substitution of both TM domains attenuates effects on nAChR expression. A minimum linker length between TM domains is needed for α7 enhancement but not for α4β2 inhibition. A combination of increased α7 steady-state levels, facilitated transport, and reduced receptor internalization accounts for hRIC-3-mediated enhancement of α7 membrane expression. RIC-3 is expressed in SH-SY5Y and PC12 cells and is induced upon differentiation; immunohistochemistry localizes it to rat brain regions co-expressing α7 nAChRs. In vitro translation/membrane insertion assay, TM domain substitution mutagenesis, immunohistochemistry, Western blot Journal of neurochemistry Medium 18179477
2008 The coiled-coil domain (CC-I) of C. elegans RIC-3 mediates receptor-specific interactions: it promotes maturation of specific nAChRs expressed in body-wall muscle but is dispensable for other nAChR subtypes. Co-immunoprecipitation confirms CC-I enhances RIC-3 affinity for specific nAChRs. Alternative splicing generates RIC-3 isoforms lacking CC-I or the entire C-terminus, enabling subtype-specific regulation. In vivo C. elegans deletion mutant analysis, co-immunoprecipitation, Xenopus oocyte heterologous expression electrophysiology Molecular biology of the cell High 19116311
2008 Drosophila RIC-3 nAChR chaperone activity does not require the coiled-coil domain (encoded by exon 7). An extra exon (exon 2) within a proline-rich N-terminal region greatly reduces chaperone activity. Host-cell-specific factors modulate RIC-3 chaperone efficiency: DmRIC-3 is more efficient in Drosophila cells, whereas human RIC-3 is more efficient in human cells, indicating cell-type-specific modulatory proteins. Cloning of 11 alternative splice isoforms, co-expression electrophysiology in Drosophila and human cell lines Journal of neurochemistry Medium 18208544
2009 Mouse RIC-3 is targeted to the ER by a cleavable N-terminal signal sequence (first 31 aa). The mature protein is a single-pass type I 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 required for homotypic self-association of RIC-3 molecules, which is necessary for efficient α7 assembly, but the coiled-coil is not required for RIC-3–α7 interaction itself. The lumenal segment and the coiled-coil domain (but not the long C-terminal tail) are required for facilitating α7 surface expression. Signal sequence analysis, protease protection/topology assay, co-immunoprecipitation, deletion/domain mutagenesis, surface expression assays in mammalian cells The Journal of neuroscience High 19812337
2009 BATH-42, a BTB-MATH domain-containing protein, interacts with RIC-3 (shown in yeast two-hybrid and in vitro). BATH-42 also interacts with the CUL-3 ubiquitin ligase complex. Loss of BATH-42 increases RIC-3 expression and decreases nAChR activity; overexpression of BATH-42 is also detrimental in a CUL-3-dependent and RIC-3 C-terminus-dependent manner. The data indicate BATH-42 targets RIC-3 for degradation via CUL-3-mediated ubiquitylation, thereby regulating RIC-3 levels. Yeast two-hybrid, in vitro interaction assay, C. elegans genetic loss-of-function/overexpression, electrophysiology Journal of cell science High 19223395
2009 Conserved residues in the second RIC-3 transmembrane domain are required for interactions with DEG-3/DES-2 and ACR-16 nAChRs, but additional domains also contribute. The relative contribution of the second TM domain vs. other domains differs between the two receptors, suggesting RIC-3 (predicted intrinsically disordered) adopts different conformations to interact with different receptors/subunits. Co-immunoprecipitation with domain deletion/point mutants in C. elegans and Xenopus oocytes, surface expression assays Biochemistry Medium 19899809
2010 Ric-3 can promote OR inhibit cell-surface delivery of α7 nAChRs (BgtRs) depending on expression level. At low levels, Ric-3 promotes α7 assembly, ER release, and surface delivery without trafficking from the ER itself. At high levels, Ric-3 suppresses surface delivery but not assembly, retaining BgtRs in the ER or in Ric-3-containing aggregates. In neurons, Ric-3 and α7 subunits are restricted to somata and dendrites (not axons) of inhibitory interneurons; Ric-3 traffics with α7 in vesicles to dendrites where it is restricted to the ER subcompartment, suggesting ER retention promotes dendritic transport. PC12 and cultured neuron live imaging, immunolocalization, co-trafficking experiments, surface BgtR binding assays The Journal of neuroscience High 20668195
2010 RIC-3 directly interacts with 5-HT3A, -C, -D, and -E subunits (co-localization in ER and co-immunoprecipitation), but exclusively enhances surface expression of homomeric 5-HT3A receptors in HEK293 cells. Increases in functional response (Emax) correlate with increased surface receptor levels (Bmax for [3H]GR65630 binding) and increased surface 5-HT3A as measured by flow cytometry. Co-immunoprecipitation, co-localization by immunocytochemistry, Ca2+ influx assays, radioligand binding, flow cytometry in HEK293 cells The Journal of biological chemistry High 20522555
2013 RIC-3 increases assembly and cell-surface trafficking of α7 receptors but does not alter α7 protein expression levels in HEK293T cells. In contrast, RIC-3 does not affect α4β2 receptor assembly but increases α4 and β2 subunit protein expression. When co-expressed with α4β2 receptors, RIC-3 prevents nicotine-induced upregulation of α4β2 receptors (assessed by FRET between subunits). FRET microscopy with fluorescent protein-tagged subunits, surface trafficking assays in HEK293T cells BMC neuroscience Medium 23586521
2016 Phosphorylation of RIC-3 at Ser-164 in C. elegans increases muscle excitability. This phosphorylation is regulated by the phosphatase calcineurin (TAX-6) and casein kinase II homologue KIN-10. Effects of calcineurin downregulation and phosphorylated RIC-3 on excitability are mediated by GABAA receptor inhibition. Thus, phosphorylated RIC-3 influences not only nAChRs but also GABAA receptors, enabling coordinated regulation of excitation-inhibition balance. C. elegans in vivo phosphorylation analysis, genetic epistasis with calcineurin and casein kinase II mutants, electrophysiology Molecular biology of the cell Medium 27489343
2016 RIC-3 expression level and splicing (generating multiple conserved isoforms) affect nAChR functional expression in brain and immune cells. In immune cells, RIC-3 expression and splicing are dynamically regulated by inflammatory signals. siRNA-mediated silencing of RIC3 in mouse macrophages eliminates the anti-inflammatory effects of cholinergic agonists, placing RIC3 as required for functional α7 nAChR-mediated cholinergic anti-inflammatory signaling. In situ hybridization, qRT-PCR, Xenopus oocyte electrophysiology, siRNA knockdown in macrophages with functional anti-inflammatory readout Molecular brain Medium 27129882
2016 Two RIC3 missense variants (P57T and V168L) identified in Parkinson's disease patients act as dominant negatives in PC12 cells: they reduce endogenous CHRNA7 (α7 nAChR subunit) levels in membrane fractions and decrease co-localization profiles compared to wild-type RIC3, suggesting impaired chaperone-mediated receptor trafficking to the plasma membrane. Transfection of mutant RIC3 in differentiated PC12 cells, Western blot of membrane fractions, confocal co-localization Journal of medical genetics Medium 27055476
2019 The intracellular domain (ICD) of 5-HT3A is required for its interaction with RIC-3. A 24-amino-acid-long segment within the 5-HT3A ICD is the molecular determinant for the RIC-3–5-HT3A interaction, identified using MBP-fused ICD deletion constructs in a RIC-3 affinity pull-down assay. Recombinant MBP-fused 5-HT3A ICD deletion constructs, RIC-3 affinity pull-down assay with purified proteins Biophysical journal Medium 31870537
2023 Two residues in nematode ACR-16 nAChR (R/K159 in the cys-loop and I504 in the C-terminal tail) account for the receptor's requirement for RIC-3 in functional expression. Mutating either residue in a non-RIC-3-requiring ACR-16 (from Dracunculus medinensis) to residues found in RIC-3-requiring orthologs confers a RIC-3 requirement, demonstrating these receptor residues mediate the functional dependency on RIC-3. Chimeric receptor construction, point mutagenesis, electrophysiology in Xenopus oocytes Protein science High 37417463
2023 The RIC-3 binding motif in 5-HT3A is a duplicated sequence (DWLR…VLDR) present in both the MX-helix and the transition between the ICD MA-helix and TM segment M4. Key residues W347, R349, L353 (MX-helix) and W447, R449, L454 (MAM4 transition) are critical for RIC-3 interaction. Alanine substitutions at these positions disrupt both peptide-based and full-length 5-HT3A–RIC-3 interactions and reduce RIC-3-mediated enhancement of functional surface expression. Ala-scanning mutagenesis with synthetic peptides in pull-down assay, full-length receptor mutagenesis with surface expression functional assays The Journal of general physiology High 37026993
2024 A RIC3 variant G88R associated with exceptional backward speech decreases both cell-surface expression and functional expression of α7 nAChRs compared to wild-type RIC3. FRET analysis shows that RIC3-G88R increases interactions between RIC3 and α7 protein in the ER, suggesting excessive or prolonged ER retention underlies reduced surface expression. FRET microscopy with fluorescent protein-tagged α7 nAChR, 125I-α-bungarotoxin binding, functional assays in HEK cells Cellular and molecular life sciences Medium 38472514
2026 RIC-3 directly interacts with the 5-HT3A intracellular domain (ICD) in native cellular contexts: a recombinant 5-HT3A ICD peptide specifically pulls down RIC-3 from Xenopus oocyte plasma membrane fractions, SH-SY5Y cell ER fractions, and mouse brain tissue. RIC-3 knockdown in SH-SY5Y cells reduces both this peptide binding and surface levels of nAChR-α7 and 5-HT3A receptors. Peptide-resin pull-down assay from native tissue and cell fractions, RIC-3 siRNA 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 203 11867529
2003 Conservation within the RIC-3 gene family. Effectors of mammalian nicotinic acetylcholine receptor expression. The Journal of biological chemistry 160 12821669
2004 Ric-3 promotes functional expression of the nicotinic acetylcholine receptor alpha7 subunit in mammalian cells. The Journal of biological chemistry 137 15504725
2005 RIC-3 enhances functional expression of multiple nicotinic acetylcholine receptor subtypes in mammalian cells. Molecular pharmacology 131 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 87 15927954
2005 Cell surface expression of 5-hydroxytryptamine type 3 receptors is promoted by RIC-3. The Journal of biological chemistry 61 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 39 19812337
2008 RIC-3 and nicotinic acetylcholine receptors: biogenesis, properties, and diversity. Biotechnology journal 39 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
2021 Neuroinflammation Modulation via α7 Nicotinic Acetylcholine Receptor and Its Chaperone, RIC-3. Molecules (Basel, Switzerland) 34 34684720
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
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 30 20522555
2013 RIC-3 differentially modulates α4β2 and α7 nicotinic receptor assembly, expression, and nicotine-induced receptor upregulation. BMC neuroscience 29 23586521
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 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 22 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 16 19498422
2020 RIC3, the cholinergic anti-inflammatory pathway, and neuroinflammation. International immunopharmacology 14 32179243
2020 Why Does Knocking Out NACHO, But Not RIC3, Completely Block Expression of α7 Nicotinic Receptors in Mouse Brain? Biomolecules 14 32204458
2019 Delineating the Site of Interaction of the 5-HT3A Receptor with the Chaperone Protein RIC-3. Biophysical journal 11 31870537
2022 Speculation on How RIC-3 and Other Chaperones Facilitate α7 Nicotinic Receptor Folding and Assembly. Molecules (Basel, Switzerland) 10 35889400
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
2023 Two residues determine nicotinic acetylcholine receptor requirement for RIC-3. Protein science : a publication of the Protein Society 5 37417463
2017 RIC3 variants are not associated with Parkinson's disease in French-Canadians and French. Neurobiology of aging 5 28153381
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
2023 Binding motif for RIC-3 chaperon protein in serotonin type 3A receptors. The Journal of general physiology 2 37026993
2025 Effects of Swapping 5HT3 and α7 Residues in Chimeric Receptor Proteins on RIC3 and NACHO Chaperone Actions. Molecules (Basel, Switzerland) 1 41226195
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

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