ReviewMolecular pharmacology2015
The G protein α chaperone Ric-8 as a potential therapeutic target.
Review in Molecular pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 44 citations in OpenAlex.
- pFastBac4x: A Novel Vector for the Simultaneous Expression of Four Proteins-Expression and Purification of a G-Protein Complex as a Case Study.Molecular biotechnology · 2026Article
- Direct Activity Measurement of Heterotrimeric Gi Proteins and Gq Protein By Effector Pulldown.Bio-protocol · 2025Article
- The guanine nucleotide exchange factor Ric-8A regulates the sensitivity of constitutively active Gαq to the inhibitor YM-254890.The Journal of biological chemistry · 2025Article
- Going Rogue: Mechanisms, Regulation, and Roles of Mutationally Activated GMolecular pharmacology · 2024Review
- Latrophilin-2 mediates fluid shear stress mechanotransduction at endothelial junctions.The EMBO journal · 2024Article
- The ric-8b protein (resistance to inhibitors of cholinesterase 8b) is key to preserving contractile function in the adult heart.The Journal of biological chemistry · 2024Article
- Human Olfactory Receptor Sensor for Odor Reconstitution.Sensors (Basel, Switzerland) · 2023Review
- Structures of Ric-8B in complex with Gα protein folding clients reveal isoform specificity mechanisms.Structure (London, England : 1993) · 2023Article
- Role of G-Proteins and GPCRs in Cardiovascular Pathologies.Bioengineering (Basel, Switzerland) · 2023Review
- Strategies towards Targeting Gαi/s Proteins: Scanning of Protein-Protein Interaction Sites To Overcome Inaccessibility.ChemMedChem · 2021Review
- Stability Analysis of a Signaling Circuit with Dual Species of GTPase Switches.Bulletin of mathematical biology · 2021Article
- Structures of Gα Proteins in Complex with Their Chaperone Reveal Quality Control Mechanisms.Cell reports · 2020Article
- Ric-8A, a GEF, and a Chaperone for G Protein α-Subunits: Evidence for the Two-Faced Interface.BioEssays : news and reviews in molecular, cellular and developmental biology · 2020Article
- Structure of the G protein chaperone and guanine nucleotide exchange factor Ric-8A bound to Gαi1.Nature communications · 2020Article
- Transducin Partners Outside the Phototransduction Pathway.Frontiers in cellular neuroscience · 2020Article
- Large-scale conformational rearrangement of the α5-helix of Gα subunits in complex with the guanine nucleotide exchange factor Ric8A.The Journal of biological chemistry · 2019Article
- Balancing the Photoreceptor Proteome: Proteostasis Network Therapeutics for Inherited Retinal Disease.Genes · 2019Review
- Structural underpinnings of Ric8A function as a G-protein α-subunit chaperone and guanine-nucleotide exchange factor.Nature communications · 2019Article
- Structure, Function, and Dynamics of the Gα Binding Domain of Ric-8A.Structure (London, England : 1993) · 2019Article
- Production of Phosphorylated Ric-8A proteins using protein kinase CK2.Protein expression and purification · 2019Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Resistance to inhibitors of cholinesterase (Ric-8)A and Ric-8B are essential genes that encode positive regulators of heterotrimeric G protein α subunits. Controversy persists surrounding the precise way(s) that Ric-8 proteins affect G protein biology and signaling. Ric-8 proteins chaperone nucleotide-free Gα-subunit states during biosynthetic protein folding prior to G protein heterotrimer assembly. In organisms spanning the evolutionary window of Ric-8 expression, experimental perturbation of Ric-8 genes results in reduced functional abundances of G proteins because G protein α subunits are misfolded and degraded rapidly. Ric-8 proteins also act as Gα-subunit guanine nucleotide exchange factors (GEFs) in vitro. However, Ric-8 GEF activity could strictly be an in vitro phenomenon stemming from the ability of Ric-8 to induce partial Gα unfolding, thereby enhancing GDP release. Ric-8 GEF activity clearly differs from the GEF activity of G protein-coupled receptors (GPCRs). G protein βγ is inhibitory to Ric-8 action but obligate for receptors. It remains an open question whether Ric-8 has dual functions in cells and regulates G proteins as both a molecular chaperone and GEF. Clearly, Ric-8 has a profound influence on heterotrimeric G protein function. For this reason, we propose that Ric-8 proteins are as yet untested therapeutic targets in which pharmacological inhibition of the Ric-8/Gα protein-protein interface could serve to attenuate the effects of disease-causing G proteins (constitutively active mutants) and/or GPCR signaling. This minireview will chronicle the understanding of Ric-8 function, provide a comparative discussion of the Ric-8 molecular chaperoning and GEF activities, and support the case for why Ric-8 proteins should be considered potential targets for development of new therapies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.