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Gene Review

norpA  -  no receptor potential A

Drosophila melanogaster

Synonyms: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase, CG3620, CdkA, DIP2, Dmel\CG3620, ...
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Disease relevance of norpA

  • DGq1 stimulation of rdgB retinal degeneration in the dark was norpA-dependent [1].
  • We suggest that these alpha subunits may be involved in pertussis toxin-insensitive pathways coupled to phospholipase C [2].
  • This loss in light sensitivity reveals that post-translational farnesylation is a critical step for the formation of membrane-associated Galphabetagamma required for transmitting light activation from rhodopsin to phospholipase Cbeta [3].
  • Hormonal stimulations of calcium influx (detected by fura-2) and of an outwardly rectifying current were observed in Sf9 cells coinfected with baculoviruses encoding trpl and various heptahelical receptors for histamine, thrombin, and thromboxane A2, all known to cause phospholipase C-beta activation in mammalian cells [4].
  • Selective cleavage by Staphylococcus aureus phosphatidylinositol-specific phospholipase C (PI-PLC) was tested with Drosophila AChE radiolabeled by the photoactivatable affinity probe 3-(trifluoromethyl)-3-(m-[125I]iodophenyl)diazirine [( 125I]TID), a reagent that specifically labels the lipid moiety of glycoinositol phospholipid-anchored proteins [5].

Psychiatry related information on norpA


High impact information on norpA


Chemical compound and disease context of norpA


Biological context of norpA


Anatomical context of norpA

  • Moreover, insofar as the rhabdomeres are specialized structures for photoreception and phototransduction, specific localization of the norpA protein within these structures, in close association with the membranes, is consistent with the proposal that it has an important role in phototransduction [16].
  • Light resulted in the effective depletion of PIP(2) by phospholipase C (PLC) in approximately three or four microvilli per absorbed photon at rates exceeding approximately 150% of total microvillar phosphoinositides per second [17].
  • In an attempt to resolve this confusion we have explored the mechanism of activation of TRPL channels co-expressed with a PLC-specific muscarinic receptor in a Drosophila cell line (S2 cells) [18].
  • In these studies, an additional PLC enzyme was purified from the cytosol of squid photoreceptors and identified as a 70-kDa protein by SDS-polyacrylamide gel electrophoresis [19].
  • However, the norpA antiserum also recognizes a 130-kDa protein in adult legs, thorax, and male abdomen, but not female abdomen [20].

Associations of norpA with chemical compounds


Physical interactions of norpA

  • G proteins of the Gq/11 subfamily functionally couple cell surface receptors to phospholipase C beta (PLC beta) isoforms [22].
  • TRP channels also appear to exist in the context of a macromolecular complex containing key components involved in activation such as phospholipase Cbeta and protein kinase C. This complex may be important for activation [24].
  • We have determined the crystal structure of the N-terminal PDZ domain of InaD bound to a peptide corresponding to the C-terminus of NorpA to 1.8 A resolution [25].
  • The rhodopsin/arrestin complexes generated in PLC mutants induce massive retinal degeneration [26].

Enzymatic interactions of norpA


Regulatory relationships of norpA

  • In the present study we show that the Calliphora rpa mutant, which has previously been hypothesized to represent an equivalent of Drosophila norpA mutants, has normal amounts of norpA mRNA but fails to express inaD mRNA [28].
  • Recent evidence is reviewed suggesting that Drosophila TRP channels are activated by one or more lipid products of PLC activity: namely diacylglycerol (DAG), its metabolites (polyunsaturated fatty acids) or the reduction in phosphatidylinositol 4,5-bisphosphate (PIP(2)) [29].
  • We have previously purified a 140-kDa PLC enzyme from squid photoreceptors that is regulated by squid Gq [19].
  • The phosphorylation of this arrestin-like protein in vivo may therefore be triggered by a Ca2+ signal that is likely to be regulated by light-activated phosphoinositide-specific phospholipase C [30].
  • Reconstitution of purified squid PLC with an AlF(-)-activated 44-kDa G protein alpha subunit extracted from squid photoreceptor membranes resulted in a significant increase in PIP2 hydrolysis over a range of Ca2+ concentrations while reconstitution with mammalian Gt alpha or Gi 1 alpha was without effect [31].

Other interactions of norpA

  • Two distantly positioned PDZ domains mediate multivalent INAD-phospholipase C interactions essential for G protein-coupled signaling [14].
  • Rescue of light responses in the Drosophila "null" phospholipase C mutant, norpAP24, by the diacylglycerol kinase mutant, rdgA, and by metabolic inhibition [32].
  • Transgenic flies were generated by germline transformation of a null norpA mutant using a P-element construct containing the wild-type norpA cDNA driven by the ninaE promoter [12].
  • The Drosophila norpA gene encodes at least two subtypes of phospholipase C (PLC), one of which is essential for phototransduction and the other is utilized in signalling pathways other than phototransduction [33].
  • In addition, PLC-beta3 specifically interacts with E3KARP, another protein closely related to NHERF, through its C-terminal PDZ-binding motif [34].

Analytical, diagnostic and therapeutic context of norpA


  1. 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]
  2. G protein diversity: a distinct class of alpha subunits is present in vertebrates and invertebrates. Strathmann, M., Simon, M.I. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  3. Targeted mutagenesis of the farnesylation site of Drosophila Ggammae disrupts membrane association of the G protein betagamma complex and affects the light sensitivity of the visual system. Schillo, S., Belusic, G., Hartmann, K., Franz, C., Kühl, B., Brenner-Weiss, G., Paulsen, R., Huber, A. J. Biol. Chem. (2004) [Pubmed]
  4. The Drosophila cation channel trpl expressed in insect Sf9 cells is stimulated by agonists of G-protein-coupled receptors. Harteneck, C., Obukhov, A.G., Zobel, A., Kalkbrenner, F., Schultz, G. FEBS Lett. (1995) [Pubmed]
  5. Drosophila acetylcholinesterase: demonstration of a glycoinositol phospholipid anchor and an endogenous proteolytic cleavage. Haas, R., Marshall, T.L., Rosenberry, T.L. Biochemistry (1988) [Pubmed]
  6. Requirement for a phospholipase C in odor response: overlap between olfaction and vision in Drosophila. Riesgo-Escovar, J., Raha, D., Carlson, J.R. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  7. The Drosophila light-activated conductance is composed of the two channels TRP and TRPL. Niemeyer, B.A., Suzuki, E., Scott, K., Jalink, K., Zuker, C.S. Cell (1996) [Pubmed]
  8. Recent insights in phosphatidylinositol signaling. Majerus, P.W., Ross, T.S., Cunningham, T.W., Caldwell, K.K., Jefferson, A.B., Bansal, V.S. Cell (1990) [Pubmed]
  9. Isolation of a putative phospholipase C gene of Drosophila, norpA, and its role in phototransduction. Bloomquist, B.T., Shortridge, R.D., Schneuwly, S., Perdew, M., Montell, C., Steller, H., Rubin, G., Pak, W.L. Cell (1988) [Pubmed]
  10. Genetic and molecular studies of olfaction in Drosophila. Hekmat-Scafe, D.S., Carlson, J.R. Ciba Found. Symp. (1996) [Pubmed]
  11. cDNA sequence and gene locus of the human retinal phosphoinositide-specific phospholipase-C beta 4 (PLCB4). Alvarez, R.A., Ghalayini, A.J., Xu, P., Hardcastle, A., Bhattacharya, S., Rao, P.N., Pettenati, M.J., Anderson, R.E., Baehr, W. Genomics (1995) [Pubmed]
  12. Molecular, biochemical, and electrophysiological characterization of Drosophila norpA mutants. Pearn, M.T., Randall, L.L., Shortridge, R.D., Burg, M.G., Pak, W.L. J. Biol. Chem. (1996) [Pubmed]
  13. Insights on trp channels from in vivo studies in Drosophila. Minke, B., Parnas, M. Annu. Rev. Physiol. (2006) [Pubmed]
  14. Two distantly positioned PDZ domains mediate multivalent INAD-phospholipase C interactions essential for G protein-coupled signaling. van Huizen, R., Miller, K., Chen, D.M., Li, Y., Lai, Z.C., Raab, R.W., Stark, W.S., Shortridge, R.D., Li, M. EMBO J. (1998) [Pubmed]
  15. Light-induced pigment granule migration in the retinular cells of Drosophila melanogaster. Comparison of wild type with ERG-defective mutants. Lo, M.V., Pak, W.L. J. Gen. Physiol. (1981) [Pubmed]
  16. Properties of photoreceptor-specific phospholipase C encoded by the norpA gene of Drosophila melanogaster. Schneuwly, S., Burg, M.G., Lending, C., Perdew, M.H., Pak, W.L. J. Biol. Chem. (1991) [Pubmed]
  17. In vivo light-induced and basal phospholipase C activity in Drosophila photoreceptors measured with genetically targeted phosphatidylinositol 4,5-bisphosphate-sensitive ion channels (Kir2.1). Hardie, R.C., Gu, Y., Martin, F., Sweeney, S.T., Raghu, P. J. Biol. Chem. (2004) [Pubmed]
  18. Activation of heterologously expressed Drosophila TRPL channels: Ca2+ is not required and InsP3 is not sufficient. Hardie, R.C., Raghu, P. Cell Calcium (1998) [Pubmed]
  19. Purification, G protein activation, and partial amino acid sequence of a novel phospholipase C from squid photoreceptors. Mitchell, J., Mayeenuddin, L.H. Biochemistry (1998) [Pubmed]
  20. Tissue-specific expression of phospholipase C encoded by the norpA gene of Drosophila melanogaster. Zhu, L., McKay, R.R., Shortridge, R.D. J. Biol. Chem. (1993) [Pubmed]
  21. Evidence for indirect control of phospholipase C (PLC-beta) by retinoids in Drosophila phototransduction. Shim, K., Zavarella, K.M., Thomas, C.F., Shortridge, R.D., Stark, W.S. Mol. Vis. (2001) [Pubmed]
  22. Direct activation of trpl cation channels by G alpha11 subunits. Obukhov, A.G., Harteneck, C., Zobel, A., Harhammer, R., Kalkbrenner, F., Leopoldt, D., Lückhoff, A., Nürnberg, B., Schultz, G. EMBO J. (1996) [Pubmed]
  23. Phosphoinositide-mediated phototransduction in Drosophila photoreceptors: the role of Ca2+ and trp. Hardie, R.C., Minke, B. Cell Calcium (1995) [Pubmed]
  24. Regulation of Drosophila TRPC channels by protein and lipid interactions. Raghu, P. Semin. Cell Dev. Biol. (2006) [Pubmed]
  25. Functional relevance of the disulfide-linked complex of the N-terminal PDZ domain of InaD with NorpA. Kimple, M.E., Siderovski, D.P., Sondek, J. EMBO J. (2001) [Pubmed]
  26. Loss of the phospholipase C gene product induces massive endocytosis of rhodopsin and arrestin in Drosophila photoreceptors. Orem, N.R., Dolph, P.J. Vision Res. (2002) [Pubmed]
  27. InsP3 receptor is essential for growth and differentiation but not for vision in Drosophila. Acharya, J.K., Jalink, K., Hardy, R.W., Hartenstein, V., Zuker, C.S. Neuron (1997) [Pubmed]
  28. The Calliphora rpa mutant lacks the PDZ domain-assembled INAD signalling complex. Huber, A., Belusic, G., Da Silva, N., Bähner, M., Gerdon, G., Draslar, K., Paulsen, R. Eur. J. Neurosci. (2000) [Pubmed]
  29. TRP channels in Drosophila photoreceptors: the lipid connection. Hardie, R.C. Cell Calcium (2003) [Pubmed]
  30. A 49-kilodalton phosphoprotein in the Drosophila photoreceptor is an arrestin homolog. Yamada, T., Takeuchi, Y., Komori, N., Kobayashi, H., Sakai, Y., Hotta, Y., Matsumoto, H. Science (1990) [Pubmed]
  31. Purification, characterization, and partial amino acid sequence of a G protein-activated phospholipase C from squid photoreceptors. Mitchell, J., Gutierrez, J., Northup, J.K. J. Biol. Chem. (1995) [Pubmed]
  32. Rescue of light responses in the Drosophila "null" phospholipase C mutant, norpAP24, by the diacylglycerol kinase mutant, rdgA, and by metabolic inhibition. Hardie, R.C., Martin, F., Chyb, S., Raghu, P. J. Biol. Chem. (2003) [Pubmed]
  33. Substitution of a non-retinal phospholipase C in Drosophila phototransduction. Kim, S., Chen, D.M., Zavarella, K., Fourtner, C.F., Stark, W.S., Shortridge, R.D. Insect Mol. Biol. (2003) [Pubmed]
  34. The roles of PDZ-containing proteins in PLC-beta-mediated signaling. Suh, P.G., Hwang, J.I., Ryu, S.H., Donowitz, M., Kim, J.H. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  35. Phospholipase C rescues visual defect in norpA mutant of Drosophila melanogaster. McKay, R.R., Chen, D.M., Miller, K., Kim, S., Stark, W.S., Shortridge, R.D. J. Biol. Chem. (1995) [Pubmed]
  36. Characteristics of Drosophila rhodopsin in wild-type and norpA vision transduction mutants. Ostroy, S.E. J. Gen. Physiol. (1978) [Pubmed]
  37. Microphotometric, ultrastructural, and electrophysiological analyses of light-dependent processes on visual receptors in white-eyed wild-type and norpA (no receptor potential) mutant Drosophila. Zinkl, G.M., Maier, L., Studer, K., Sapp, R., Chen, D.M., Stark, W.S. Vis. Neurosci. (1990) [Pubmed]
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