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Gene Review

F46C5.9  -  Protein F46C5.9

Caenorhabditis elegans

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Disease relevance of G-protein


Psychiatry related information on G-protein


High impact information on G-protein

  • In C. elegans, gpb-1 encodes the sole Gbeta subunit; therefore, its inactivation should affect all heterotrimeric G protein signaling [5].
  • Different G-protein signaling pathways have characteristic effects on behavior, neuronal degeneration, and embryonic development [6].
  • On the basis of epistasis analysis, flp-1 gene products appear to signal upstream of a G protein-coupled second messenger system [7].
  • Asymmetric division of Drosophila neuroblasts (NBs) and the Caenorhabditis elegans zygote uses polarity cues provided by the Par proteins, as well as heterotrimeric G-protein-signalling that is activated by a receptor-independent mechanism mediated by GoLoco/GPR motif proteins [8].
  • G protein-coupled receptor kinases (GRKs) are important regulators of G protein signal transduction that specifically phosphorylate activated GPCRs to terminate signaling [9].

Biological context of G-protein


Anatomical context of G-protein

  • Finally, the response to NaCl is modulated by G-protein signalling in the ASI and ADF neurons, a second G-protein pathway in ASH and cGMP signalling in neurons exposed to the body fluid [15].
  • These channels, as well as the G-protein Galpha(o), function in neuroendocrine cells to promote release of neurotransmitters that block egg laying until eggs filling the uterus deform the neuroendocrine cells [16].
  • Electrophysiological analyses using the Xenopus oocyte system showed that all three GAR-2 isoforms couple to the activation of G-protein-gated inwardly rectifying K+ (GIRK1) channel with similar drug specificity [12].
  • Modulation of EGF receptor-mediated vulva development by the heterotrimeric G-protein Galphaq and excitable cells in C. elegans [17].
  • Muscarinic acetylcholine receptors regulate the activity of neurons and muscle cells through G-protein-coupled cascades [18].

Associations of G-protein with chemical compounds

  • Among the three G-protein-linked acetylcholine receptors (GARs) in Caenorhabditis elegans (C. elegans), GAR-3 is structurally and pharmacologically most similar to mammalian muscarinic acetylcholine receptors (mAChRs) [19].
  • A gene encoding the alpha-subunit of a guanine nucleotide binding regulatory protein (G-protein) was isolated from a library of genomic Caenorhabditis elegans DNA [20].
  • Receptor signaling studies with mammalian AV12 cells expressing the 5HT1Hc-receptor and the promiscuous G-protein, Galpha15, demonstrated dose-dependent intracellular signals with serotonin acting as an agonist [21].
  • mGluRs (metabotropic glutamate receptors) are G-protein-coupled receptors that play an important neuromodulatory role in the brain [22].
  • Finally, we found that a knock-out for the HSN-expressed receptor G-protein-coupled acetylcholine receptor 2 (GAR-2) shows a partial defect in the inhibition of egg laying and fails to respond to aldicarb [23].

Physical interactions of G-protein


Other interactions of G-protein

  • The signaling cascade is only partially dependent on the phospholipase C beta (EGL-8) and is negatively regulated by G alpha(o) [GOA-1 (G-protein, O, alpha subunit family member 1)] and calcium/calmodulin-dependent kinase [UNC-43 (uncoordinated family member 43)] [26].
  • Here we show that the same Ca2+/MAPK pathway promotes str-2 expression in the AWC and ASI neurons together with multiple cell-autonomous and noncell-autonomous G-protein-signaling pathways [11].
  • The G-protein gamma subunit gpc-1 of the nematode C.elegans is involved in taste adaptation [27].
  • Here, we describe the characterization of the second G-protein beta-subunit gene gpb-2 [28].
  • GAR-3 signaling is enhanced in worms overexpressing gar-3 or lacking GPB-2, a G-protein beta-subunit involved in RGS-mediated inhibition of G(o)alpha- and G(q)alpha-linked pathways [18].

Analytical, diagnostic and therapeutic context of G-protein

  • G-protein expression in infective larvae was also investigated by RT-PCR analysis: this stage of the organism was found to resemble the adult more than the microfilaria but differed from the adult in that GS was absent and Gi3 was present [29].
  • No other G-protein alpha-subunits were found in microfilariae by Western blotting [29].


  1. Altered behaviour following RNA interference knockdown of a C. elegans G-protein coupled receptor by ingested double stranded RNA. Vaz Gomes, A., Wahlestedt, C. Eur. J. Pharmacol. (2000) [Pubmed]
  2. Mimicry of a G protein mutation by pertussis toxin expression in transgenic Caenorhabditis elegans. Darby, C., Falkow, S. Infect. Immun. (2001) [Pubmed]
  3. The C. elegans G-protein-coupled receptor SRA-13 inhibits RAS/MAPK signalling during olfaction and vulval development. Battu, G., Hoier, E.F., Hajnal, A. Development (2003) [Pubmed]
  4. Natural variation in a neuropeptide Y receptor homolog modifies social behavior and food response in C. elegans. de Bono, M., Bargmann, C.I. Cell (1998) [Pubmed]
  5. G proteins are required for spatial orientation of early cell cleavages in C. elegans embryos. Zwaal, R.R., Ahringer, J., van Luenen, H.G., Rushforth, A., Anderson, P., Plasterk, R.H. Cell (1996) [Pubmed]
  6. Signal transduction in the Caenorhabditis elegans nervous system. Bargmann, C.I., Kaplan, J.M. Annu. Rev. Neurosci. (1998) [Pubmed]
  7. Disruption of a neuropeptide gene, flp-1, causes multiple behavioral defects in Caenorhabditis elegans. Nelson, L.S., Rosoff, M.L., Li, C. Science (1998) [Pubmed]
  8. Ric-8 controls Drosophila neural progenitor asymmetric division by regulating heterotrimeric G proteins. Wang, H., Ng, K.H., Qian, H., Siderovski, D.P., Chia, W., Yu, F. Nat. Cell Biol. (2005) [Pubmed]
  9. G protein-coupled receptor kinase function is essential for chemosensation in C. elegans. Fukuto, H.S., Ferkey, D.M., Apicella, A.J., Lans, H., Sharmeen, T., Chen, W., Lefkowitz, R.J., Jansen, G., Schafer, W.R., Hart, A.C. Neuron (2004) [Pubmed]
  10. Characterization of a G-protein beta-subunit gene from the nematode Caenorhabditis elegans. van der Voorn, L., Gebbink, M., Plasterk, R.H., Ploegh, H.L. J. Mol. Biol. (1990) [Pubmed]
  11. Noncell- and cell-autonomous G-protein-signaling converges with Ca2+/mitogen-activated protein kinase signaling to regulate str-2 receptor gene expression in Caenorhabditis elegans. Lans, H., Jansen, G. Genetics (2006) [Pubmed]
  12. Three functional isoforms of GAR-2, a Caenorhabditis elegans G-protein-linked acetylcholine receptor, are produced by alternative splicing. Suh, S.J., Park, Y.S., Lee, Y.S., Cho, T.J., Kaang, B.K., Cho, N.J. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  13. Two large families of chemoreceptor genes in the nematodes Caenorhabditis elegans and Caenorhabditis briggsae reveal extensive gene duplication, diversification, movement, and intron loss. Robertson, H.M. Genome Res. (1998) [Pubmed]
  14. A Metabotropic Glutamate Receptor Family Gene in Dictyostelium discoideum. Taniura, H., Sanada, N., Kuramoto, N., Yoneda, Y. J. Biol. Chem. (2006) [Pubmed]
  15. Antagonistic sensory cues generate gustatory plasticity in Caenorhabditis elegans. Hukema, R.K., Rademakers, S., Dekkers, M.P., Burghoorn, J., Jansen, G. EMBO J. (2006) [Pubmed]
  16. A Specific Subset of Transient Receptor Potential Vanilloid-Type Channel Subunits in Caenorhabditis elegans Endocrine Cells Function as Mixed Heteromers to Promote Neurotransmitter Release. Jose, A.M., Bany, I.A., Chase, D.L., Koelle, M.R. Genetics (2007) [Pubmed]
  17. Modulation of EGF receptor-mediated vulva development by the heterotrimeric G-protein Galphaq and excitable cells in C. elegans. Moghal, N., Garcia, L.R., Khan, L.A., Iwasaki, K., Sternberg, P.W. Development (2003) [Pubmed]
  18. The GAR-3 muscarinic receptor cooperates with calcium signals to regulate muscle contraction in the Caenorhabditis elegans pharynx. Steger, K.A., Avery, L. Genetics (2004) [Pubmed]
  19. Stimulation of cyclic AMP production by the Caenorhabditis elegans muscarinic acetylcholine receptor GAR-3 in Chinese hamster ovary cells. Park, Y.S., Cho, T.J., Cho, N.J. Arch. Biochem. Biophys. (2006) [Pubmed]
  20. Characterization of a G-protein alpha-subunit gene from the nematode Caenorhabditis elegans. Fino Silva, I., Plasterk, R.H. J. Mol. Biol. (1990) [Pubmed]
  21. Characterization of a novel G-protein coupled receptor from the parasitic nematode H. contortus with high affinity for serotonin. Smith, M.W., Borts, T.L., Emkey, R., Cook, C.A., Wiggins, C.J., Gutierrez, J.A. J. Neurochem. (2003) [Pubmed]
  22. Molecular characterization of the metabotropic glutamate receptor family in Caenorhabditis elegans. Dillon, J., Hopper, N.A., Holden-Dye, L., O'connor, V. Biochem. Soc. Trans. (2006) [Pubmed]
  23. Genetic and cellular basis for acetylcholine inhibition of Caenorhabditis elegans egg-laying behavior. Bany, I.A., Dong, M.Q., Koelle, M.R. J. Neurosci. (2003) [Pubmed]
  24. Antagonistic pathways in neurons exposed to body fluid regulate social feeding in Caenorhabditis elegans. Coates, J.C., de Bono, M. Nature (2002) [Pubmed]
  25. An interneuronal chemoreceptor required for olfactory imprinting in C. elegans. Remy, J.J., Hobert, O. Science (2005) [Pubmed]
  26. Starvation induces cAMP response element-binding protein-dependent gene expression through octopamine-Gq signaling in Caenorhabditis elegans. Suo, S., Kimura, Y., Van Tol, H.H. J. Neurosci. (2006) [Pubmed]
  27. The G-protein gamma subunit gpc-1 of the nematode C.elegans is involved in taste adaptation. Jansen, G., Weinkove, D., Plasterk, R.H. EMBO J. (2002) [Pubmed]
  28. The G-protein beta-subunit GPB-2 in Caenorhabditis elegans regulates the G(o)alpha-G(q)alpha signaling network through interactions with the regulator of G-protein signaling proteins EGL-10 and EAT-16. van der Linden, A.M., Simmer, F., Cuppen, E., Plasterk, R.H. Genetics (2001) [Pubmed]
  29. Acanthocheilonema viteae: stage-specific expression of G-protein alpha-subunits. Grant, K.R., Harnett, M.M., Harnett, W. Exp. Parasitol. (1997) [Pubmed]
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