Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi


  • Gregory G. TallEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_171


Historical Background

Discovery of Ric-8 proteins: The Caenorhabditis elegans RIC-8 gene and a homologous mouse gene that was later termed Ric-8A (or a synembryn) were discovered by Miller and Rand using a genetic screen to obtain C. elegans mutants that were resistant to the inhibitor of cholinesterase, aldicarb (Miller et al. 1996). Aldicarb treatment of wild-type worms leads to neurotoxic accumulation of postsynaptic acetylcholine and subsequent death. Ric mutants lived in the presence of aldicarb because they contained gene defects that restored normal acetylcholine levels, primarily by decreasing neurotransmitter secretion or release. Through epistasis analyses, the gene complementing the ric-8 mutant allele was predicted to elicit action upstream of or parallel to the gene encoding G protein α q in a diacylglycerol-dependent synaptic-vesicle-priming pathway (Miller et al. 2000). Miller and Rand...

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  1. Afshar K, Willard FS, Colombo K, Siderovski DP, Gonczy P. Cortical localization of the Gα protein GPA-16 requires RIC-8 function during C. elegans asymmetric cell division. Development. 2005;132(20):4449–59.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Ali BR, Seabra MC. Targeting of Rab GTPases to cellular membranes. Biochem Soc Trans. 2005;33:652–6.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Blumer JB, Kuriyama R, Gettys TW, Lanier SM. The G-protein regulatory (GPR) motif-containing Leu-Gly-Asn-enriched protein (LGN) and Giα3 influence cortical positioning of the mitotic spindle poles at metaphase in symmetrically dividing mammalian cells. Eur J Cell Biol. 2006;85(12):1233–40.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Chisari M, Saini DK, Kalyanaraman V, Gautam N. Shuttling of G Protein subunits between the plasma membrane and intracellular membranes. J Biol Chem. 2007;282(33):24092–8.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Cho H, Kehrl JH. Localization of Giα proteins in the centrosomes and at the midbody: implication for their role in cell division. J Cell Biol. 2007;178(2):245–55.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Du Q, Macara IG. Mammalian pins is a conformational switch that links NuMA to heterotrimeric G proteins. Cell. 2004;119(4):503–16.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Du Q, Taylor L, Compton DA, Macara IG. LGN blocks the ability of NuMA to bind and stabilize microtubules: a mechanism for mitotic spindle assembly regulation. Curr Biol. 2002;12(22):1928–33.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Dupre DJ, Robitaille M, Richer M, Ethier N, Mamarbachi AM, Hebert TE. Dopamine receptor-interacting protein 78 acts as a molecular chaperone for Gγ subunits before assembly with Gβ. J Biol Chem. 2007;282(18):13703–15.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Hampoelz B, Hoeller O, Bowman SK, Dunican D, Knoblich JA. Drosophila Ric-8 is essential for plasma-membrane localization of heterotrimeric G proteins. Nat Cell Biol. 2005;7(11):1099–105.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Hess HA, Roper J-C, Grill SW, Koelle MR. RGS-7 completes a receptor-independent heterotrimeric G protein cycle to asymmetrically regulate mitotic spindle positioning in C. elegans. Cell. 2004;119(2):209–18.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Kerr DS, Von Dannecker LEC, Davalos M, Michaloski JS, Malnic B. Ric-8B interacts with Gαolf and Gγ13 and colocalizes with Gαolf, Gβ1 and Gγ13 in the cilia of olfactory sensory neurons. Mol Cell Neurosci. 2008;38:341–8.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Klattenhoff C, Montecino M, Soto X, Guzmen L, Romo X, de los Angeles Garcia M, et al. Human brain synembryn interacts with Gsα and Gqα and is translocated to the plasma membrane in response to isoproterenol and carbachol. J Cell Physiol. 2003;195(2):151–7.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Lukov GL, Hu T, McLaughlin JN, Hamm HE, Willardson BM. Phosducin-like protein acts as a molecular chaperone for G protein βγ dimer assembly. EMBO J. 2005;24(11):1965–75.  https://doi.org/10.1038/sj.emboj.7600673.CrossRefPubMedPubMedCentralGoogle Scholar
  14. Marrari Y, Crouthamel M, Irannejad R, Wedegaertner PB. Assembly and trafficking of heterotrimeric G proteins. Biochemistry. 2007;46(26):7665–77.  https://doi.org/10.1021/bi700338m.CrossRefPubMedPubMedCentralGoogle Scholar
  15. Matsuzaki F. Drosophila G-protein signaling: intricate roles for Ric-8? Nat Cell Biol. 2005;7(11):1047–9.  https://doi.org/10.1038/ncb1105-1047.CrossRefPubMedPubMedCentralGoogle Scholar
  16. Miller KG, Rand JBA. role for RIC-8 (Synembryn) and GOA-1 (Goα) in regulating a subset of centrosome movements during early embryogenesis in Caenorhabditis elegans. Genetics. 2000;156(4):1649–60.PubMedPubMedCentralGoogle Scholar
  17. Miller KG, Alfonso A, Nguyen M, Crowell JA, Johnson CD, Rand JB. A genetic selection for Caenorhabditis elegans synaptic transmission mutants. Proc Natl Acad Sci. 1996;93(22):12593–8.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Miller KG, Emerson MD, McManus JR, Rand JB. RIC-8 (Synembryn): a novel conserved protein that is required for Gqα signaling in the C. elegans nervous system. Neuron. 2000;27:289–99.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Nagai Y, Nishimura A, Tago K, Mizuno N, Itoh H. Ric-8B stabilizes the alpha subunit of stimulatory G protein by inhibiting its ubiquitination. J Biol Chem. 2010;285(15):11114–20.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Reynolds NK, Schade MA, Miller KG. Convergent, RIC-8-dependent Gα signaling pathways in the Caenorhabditis elegans synaptic signaling network. Genetics. 2005;169(2):651–70.PubMedPubMedCentralCrossRefGoogle Scholar
  21. Romo X, Pasten P, MartÌnez S, Soto X, Lara P, ARd A, et al. xRic-8 is a GEF for Gsα and participates in maintaining meiotic arrest in Xenopus laevis oocytes. J Cell Physiol. 2008;214(3):673–80.PubMedPubMedCentralCrossRefGoogle Scholar
  22. Schade MA, Reynolds NK, Dollins CM, Miller KG. Mutations that rescue the paralysis of Caenorhabditis elegans ric-8 (Synembryn) mutants activate the Gαs pathway and define a third major branch of the synaptic signaling network. Genetics. 2005;169(2):631–49.PubMedPubMedCentralCrossRefGoogle Scholar
  23. Siderovski DP, Willard FS. The GAPs, GEFs, and GDIs of heterotrimeric G-protein alpha subunits. Int J Biol Sci. 2005;1(2):51–66.PubMedPubMedCentralCrossRefGoogle Scholar
  24. Siller KH, Doe CQ. Spindle orientation during asymmetric cell division. Nat Cell Biol. 2009;11(4):365–74.  https://doi.org/10.1038/ncb0409-365.CrossRefPubMedPubMedCentralGoogle Scholar
  25. Tall GG, Gilman AG. Resistance to inhibitors of cholinesterase 8A catalyzes release of Gαi-GTP and nuclear mitotic apparatus protein (NuMA) from NuMA/LGN/Gαi-GDP complexes. Proc Natl Acad Sci. 2005;102(46):16584–9.PubMedPubMedCentralCrossRefGoogle Scholar
  26. Tall GG, Krumins AM, Gilman AG. Mammalian Ric-8A (Synembryn) is a heterotrimeric Gα protein guanine nucleotide exchange factor. J Biol Chem. 2003;278(10):8356–62.PubMedPubMedCentralCrossRefGoogle Scholar
  27. Thomas CJ, Tall GG, Adhikari A, Sprang SR. RIC-8A catalyzes guanine nucleotide exchange on Gαi 1 bound to the GPR/GoLoco exchange inhibitor AGS3. J Biol Chem. 2008;2008:M802422200.Google Scholar
  28. Tsutsumi R, Fukata Y, Noritake J, Iwanaga T, Perez F, Fukata M. Identification of G protein α subunit-palmitoylating enzyme. Mol Cell Biol. 2009;29(2):435–47.PubMedPubMedCentralCrossRefGoogle Scholar
  29. Von Dannecker LEC, Mercadante AF, Malnic B. Ric-8B promotes functional expression of odorant receptors. PNAS. 2006;103(24):9310–4.CrossRefGoogle Scholar
  30. Wilkie TM, Kinch L. New roles for Gα and RGS proteins: communication continues despite pulling sisters apart. Curr Biol. 2005;15:R843–954.PubMedPubMedCentralCrossRefGoogle Scholar
  31. Woodard GE, Huang N-N, Cho H, Miki T, Tall GG, Kehrl JH. Ric-8A and Giα recruit LGN, NuMA, and Dynein to the cell cortex to help orient the mitotic spindle. Mol Cell Biol. 2010;30(14):3519–30.PubMedPubMedCentralCrossRefGoogle Scholar
  32. Yu F, Kuo CT, Jan YN. Drosophila neuroblast asymmetric cell division: recent advances and implications for stem cell biology. Neuron. 2006;51(1):13–20.PubMedPubMedCentralCrossRefGoogle Scholar
  33. Zhuang H, Matsunami H. Synergism of accessory factors in functional expression of mammalian odorant receptors. J Biol Chem. 2007;282:15284–93.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of Pharmacology and PhysiologyUniversity of Rochester Medical CenterRochesterUSA