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Gene Review

Galphaq  -  G protein alpha q subunit

Drosophila melanogaster

Synonyms: CG17759, DGalpha[[q]], DGalphaq, DGq, DGqalpha, ...
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Disease relevance of Galpha49B

  • These proteins represent a new class of G alpha subunits because they lack both high amino acid identity with other G alpha proteins and the pertussis toxin ADP ribosylation site [1].
  • Targeted expression of either a stimulatory (Galpha(s)) or inhibitory (Galpha(i)) Galpha subunit, or tetanus toxin light chain (TNT) in dopamine and serotonin neurons of living flies blocked behavioral sensitization to repeated cocaine exposures [2].
  • Vaccinia virus systems for expression of G alpha genes in S49 cells [3].

High impact information on Galpha49B

  • The GoLoco motif is a 19-amino-acid sequence with guanine nucleotide dissociation inhibitor activity against G-alpha subunits of the adenylyl-cyclase-inhibitory subclass [4].
  • Upon ligand binding, the transmitter receptors interact with heterotrimeric G proteins, allowing G alpha and G beta gamma subunits to disengage [5].
  • Their ability to dampen signalling via Galphai-, Galphaq- and Galpha12/13-coupled pathways makes them crucial players in mediating the multitude of cellular processes controlled by heterotrimeric G proteins [6].
  • We show here that, in Drosophila, both functions require the Galpha interaction partner Ric-8 [7].
  • During asymmetric cell division, this leads to various defects: apico-basal polarity is not maintained, mitotic spindles are misoriented and the size of the two daughter cells becomes nearly equal. ric-8 mutants also have defects in gastrulation that resemble mutants in the Galpha protein concertina or the extracellular ligand foldedgastrulation [7].

Biological context of Galpha49B


Anatomical context of Galpha49B

  • The DGq proteins immunolocalized to the ocelli and all eight retinular photoreceptor cell rhabdomeres [8].
  • Here we show, using live Drosophila flies, that light causes massive and reversible translocation of the visual Gqalpha to the cytosol, associated with marked architectural changes in the signaling compartment [9].
  • Epistatic analysis showed that Gqalpha is necessary but not sufficient to bring about the morphological changes in the signaling organelle [9].
  • We examined the in vivo splicing of dgq in adult flies and find that, in all but the male gonads, only two isoforms are expressed [10].
  • A splice variant of Galphaq, dgqalpha3, is expressed in early axonal growth cones, which go to form the commissures in the Drosophila embryonic CNS [12].

Associations of Galpha49B with chemical compounds

  • Although the role of the G alpha subunit in effector activation, guanine nucleotide exchange and GTP hydrolysis has been well studied, the cellular functions of the G beta subunits are less well understood [13].
  • In addition, we show that (i) the specific PLC activity is a key factor determining the photoreceptor sensitivity; (ii) the catalytic activity and response termination are separable functions of PLC; and (iii) a mutation in the putative G alpha-interacting C2 domain causes a preferentially strong defect in latency [14].

Physical interactions of Galpha49B

  • G beta gamma dimers bind G alpha subunits and anchor them to the membrane for presentation to the receptor [13].
  • The predicted sequence of Pins contained tetratrico-peptide repeats (TPRs) and motifs implicated in binding Galpha proteins [15].

Other interactions of Galpha49B

  • Light-dependent subcellular translocation of Gqalpha in Drosophila photoreceptors is facilitated by the photoreceptor-specific myosin III NINAC [16].
  • We propose that DRhoGEF2 uses microtubule dynamics to search for cortical subdomains of receptor-mediated Galpha activation, which in turn causes localized actomyosin contraction associated with morphogenetic movements during development [17].
  • The expressed levels of dGqalpha and itpr in the tarsus of poxn70 mutant flies were reduced compared with those of wild-type flies [18].
  • Here, we show that the abundance of DUNC-13 in NMJ synaptic boutons is regulated downstream of GalphaS and Galphaq pathways, which have inhibitory and facilitatory roles, respectively [19].
  • This set includes Galpha15, Galpha16, Galphaq, and chimeric Galphaq proteins with the last few amino acids of either Galphai2 (Galphaqi), Galphao (Galphaqo), or Galphaz (Galphaqz) [20].

Analytical, diagnostic and therapeutic context of Galpha49B


  1. dgq: a drosophila gene encoding a visual system-specific G alpha molecule. Lee, Y.J., Dobbs, M.B., Verardi, M.L., Hyde, D.R. Neuron (1990) [Pubmed]
  2. Ectopic G-protein expression in dopamine and serotonin neurons blocks cocaine sensitization in Drosophila melanogaster. Li, H., Chaney, S., Roberts, I.J., Forte, M., Hirsh, J. Curr. Biol. (2000) [Pubmed]
  3. Vaccinia virus systems for expression of G alpha genes in S49 cells. Quan, F., Forte, M. Meth. Enzymol. (1994) [Pubmed]
  4. Return of the GDI: the GoLoco motif in cell division. Willard, F.S., Kimple, R.J., Siderovski, D.P. Annu. Rev. Biochem. (2004) [Pubmed]
  5. Mediation of PACAP-like neuropeptide transmission by coactivation of Ras/Raf and cAMP signal transduction pathways in Drosophila. Zhong, Y. Nature (1995) [Pubmed]
  6. RGS proteins: more than just GAPs for heterotrimeric G proteins. De Vries, L., Gist Farquhar, M. Trends Cell Biol. (1999) [Pubmed]
  7. Drosophila Ric-8 is essential for plasma-membrane localization of heterotrimeric G proteins. Hampoelz, B., Hoeller, O., Bowman, S.K., Dunican, D., Knoblich, J.A. Nat. Cell Biol. (2005) [Pubmed]
  8. The Drosophila dgq gene encodes a G alpha protein that mediates phototransduction. Lee, Y.J., Shah, S., Suzuki, E., Zars, T., O'Day, P.M., Hyde, D.R. Neuron (1994) [Pubmed]
  9. Regulation of light-dependent Gqalpha translocation and morphological changes in fly photoreceptors. Kosloff, M., Elia, N., Joel-Almagor, T., Timberg, R., Zars, T.D., Hyde, D.R., Minke, B., Selinger, Z. EMBO J. (2003) [Pubmed]
  10. Novel Gq alpha isoform is a candidate transducer of rhodopsin signaling in a Drosophila testes-autonomous pacemaker. Alvarez, C.E., Robison, K., Gilbert, W. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  11. Gq alpha protein function in vivo: genetic dissection of its role in photoreceptor cell physiology. Scott, K., Becker, A., Sun, Y., Hardy, R., Zuker, C. Neuron (1995) [Pubmed]
  12. Altered levels of Gq activity modulate axonal pathfinding in Drosophila. Ratnaparkhi, A., Banerjee, S., Hasan, G. J. Neurosci. (2002) [Pubmed]
  13. An eye-specific G beta subunit essential for termination of the phototransduction cascade. Dolph, P.J., Man-Son-Hing, H., Yarfitz, S., Colley, N.J., Deer, J.R., Spencer, M., Hurley, J.B., Zuker, C.S. Nature (1994) [Pubmed]
  14. Specific molecular alterations in the norpA-encoded phospholipase C of Drosophila and their effects on electrophysiological responses in vivo. Yoon, J., Leung, H.T., Lee, S., Geng, C., Kim, Y., Baek, K., Pak, W.L. J. Neurochem. (2004) [Pubmed]
  15. A protein complex containing Inscuteable and the Galpha-binding protein Pins orients asymmetric cell divisions in Drosophila. Schaefer, M., Shevchenko, A., Shevchenko, A., Knoblich, J.A. Curr. Biol. (2000) [Pubmed]
  16. Light-dependent subcellular translocation of Gqalpha in Drosophila photoreceptors is facilitated by the photoreceptor-specific myosin III NINAC. Cronin, M.A., Diao, F., Tsunoda, S. J. Cell. Sci. (2004) [Pubmed]
  17. Drosophila RhoGEF2 associates with microtubule plus ends in an EB1-dependent manner. Rogers, S.L., Wiedemann, U., Häcker, U., Turck, C., Vale, R.D. Curr. Biol. (2004) [Pubmed]
  18. Inositol 1,4,5-trisphosphate transduction cascade in taste reception of the fleshfly, Boettcherisca peregrina. Koganezawa, M., Shimada, I. J. Neurobiol. (2002) [Pubmed]
  19. Synaptic Drosophila UNC-13 is regulated by antagonistic G-protein pathways via a proteasome-dependent degradation mechanism. Aravamudan, B., Broadie, K. J. Neurobiol. (2003) [Pubmed]
  20. The G protein-coupling profile of metabotropic glutamate receptors, as determined with exogenous G proteins, is independent of their ligand recognition domain. Parmentier, M.L., Joly, C., Restituito, S., Bockaert, J., Grau, Y., Pin, J.P. Mol. Pharmacol. (1998) [Pubmed]
  21. A Drosophila G-protein alpha subunit, Gf alpha, expressed in a spatially and temporally restricted pattern during Drosophila development. Quan, F., Wolfgang, W.J., Forte, M. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
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