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Gene Review

inaC  -  inactivation no afterpotential C

Drosophila melanogaster

Synonyms: CG6518, Dmel\CG6518, Dpkc2, Eye-PKC, INAC, ...
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Disease relevance of inaC


High impact information on inaC

  • Bright conditioning lights delivered to inaC photoreceptors lead to an abnormal loss of sensitivity in whole cell recordings from dissociated ommatidia; this has been interpreted as 'hyper-adaptation' and PKC's role has been suggested to be distinct from light adaptation [2].
  • Furthermore, we show that in the absence of PKC individual bumps fail to terminate normally, an effect that can account for the pleiotropic manifestations of the inaC phenotype [2].
  • We now show that under physiological conditions light adaptation is severely reduced in inaC, suggesting that eye-specific PKC, itself activated by a rise in cytosolic calcium and diacylglycerol, is required for adaptation [2].
  • These results indicate that eye-PKC functions in the light-dependent regulation of the phototransduction cascade in Drosophila [1].
  • Finally, we identify a photoreceptor-specific PKC as essential for normal kinetics of [Ca2+]i recovery [3].

Biological context of inaC

  • It is proposed that the rise of the intracellular Ca2+ concentration upon visual excitation initiates the phosphorylation of the InaD protein by eye-PKC and thereby modulates its function in the control of the light response [4].
  • We report here that extracellular calcium entering through the light-activated conductance is a key regulator of both the activation and deactivation phases of the phototransduction cascade, and that inaC mutant photoreceptors are specifically defective in the calcium-dependent deactivation mechanism [5].
  • Calcium homeostasis in photoreceptor cells of Drosophila mutants inaC and trp studied with the pupil mechanism [6].
  • In flies lacking endogenous eye-PKC (inaCp215), normal visual physiology is restored upon expression of wild-type eye-PKC, whereas the eye-PKCI700D mutant is completely inactive [7].
  • The deduced amino acid sequence of Calliphora ePKC comprises 685 amino acids (MW = 78 036) and displays 80.4% sequence identity with Drosophila ePKC [8].

Anatomical context of inaC

  • Northern blot analysis confirmed that trp, inaC and InaD transcripts were present in RNA isolated from the retina, but not in RNA isolated from brain or thorax [9].
  • Extraction of membranes with buffers of different ionic strengths suggested that the trp gene product is an integral membrane protein, whilst the inaC and InaD gene products are peripherally bound membrane proteins [9].
  • The Ca2+-dependent protein kinase C (PKC) isoform PKCalpha plays a crucial role in initiating endothelial cell contraction and disassembly of VE-cadherin junctions [10].
  • However, the modes of action of Munc-18 and PKC in vesicle transport have not been clarified [11].
  • Here, we show that recombinant Munc-18 is phosphorylated by conventional PKC in a Ca2+- and phospholipid-dependent manner in a cell-free system [11].

Associations of inaC with chemical compounds


Physical interactions of inaC

  • We previously showed that eye-PKC interacted with the second PDZ domain (PDZ2) of INAD [13].

Enzymatic interactions of inaC

  • We reveal that Ser982 of TRP is phosphorylated by eye-PKC in vitro and, importantly, in the fly eye, as shown by mass spectrometry [14].

Regulatory relationships of inaC

  • In particular, InsP3 infusion, modulation of protein kinase C activity or elevation of intracellular calcium concentration failed to induce trpl currents [15].

Other interactions of inaC

  • To identify substrates of eye-PKC, we immunoprecipitated the complex from head lysates using anti-INAD antibodies and performed in vitro kinase assays [16].
  • Moreover, deactivation is regulated by the interaction between INAD and TRP, because abrogation of this interaction in InaD(p215) results in slow deactivation similar to that of inaC(p209) lacking eye-PKC [14].
  • Both eye-PKC and DaPKC are differentially localized through tethering to multimolecular complexes [17].
  • 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 [18].
  • Dfrizzled2, Disheveled, and protein kinase C are also required [19].

Analytical, diagnostic and therapeutic context of inaC


  1. Photoreceptor deactivation and retinal degeneration mediated by a photoreceptor-specific protein kinase C. Smith, D.P., Ranganathan, R., Hardy, R.W., Marx, J., Tsuchida, T., Zuker, C.S. Science (1991) [Pubmed]
  2. Protein kinase C is required for light adaptation in Drosophila photoreceptors. Hardie, R.C., Peretz, A., Suss-Toby, E., Rom-Glas, A., Bishop, S.A., Selinger, Z., Minke, B. Nature (1993) [Pubmed]
  3. Cytosolic calcium transients: spatial localization and role in Drosophila photoreceptor cell function. Ranganathan, R., Bacskai, B.J., Tsien, R.Y., Zuker, C.S. Neuron (1994) [Pubmed]
  4. Phosphorylation of the InaD gene product, a photoreceptor membrane protein required for recovery of visual excitation. Huber, A., Sander, P., Paulsen, R. J. Biol. Chem. (1996) [Pubmed]
  5. A Drosophila mutant defective in extracellular calcium-dependent photoreceptor deactivation and rapid desensitization. Ranganathan, R., Harris, G.L., Stevens, C.F., Zuker, C.S. Nature (1991) [Pubmed]
  6. Calcium homeostasis in photoreceptor cells of Drosophila mutants inaC and trp studied with the pupil mechanism. Hofstee, C.A., Stavenga, D.G. Vis. Neurosci. (1996) [Pubmed]
  7. Interaction of eye protein kinase C and INAD in Drosophila. Localization of binding domains and electrophysiological characterization of a loss of association in transgenic flies. Adamski, F.M., Zhu, M.Y., Bahiraei, F., Shieh, B.H. J. Biol. Chem. (1998) [Pubmed]
  8. The TRP Ca2+ channel assembled in a signaling complex by the PDZ domain protein INAD is phosphorylated through the interaction with protein kinase C (ePKC). Huber, A., Sander, P., Bähner, M., Paulsen, R. FEBS Lett. (1998) [Pubmed]
  9. Isolation of genes encoding photoreceptor-specific proteins by immunoscreening with antibodies directed against purified blowfly rhabdoms. Huber, A., Sander, P., Wolfrum, U., Groell, C., Gerdon, G., Paulsen, R. J. Photochem. Photobiol. B, Biol. (1996) [Pubmed]
  10. Ca2+ Signaling, TRP Channels, and Endothelial Permeability. Tiruppathi, C., Ahmmed, G.U., Vogel, S.M., Malik, A.B. Microcirculation (New York, N.Y. : 1994) (2006) [Pubmed]
  11. Phosphorylation of Munc-18/n-Sec1/rbSec1 by protein kinase C: its implication in regulating the interaction of Munc-18/n-Sec1/rbSec1 with syntaxin. Fujita, Y., Sasaki, T., Fukui, K., Kotani, H., Kimura, T., Hata, Y., Südhof, T.C., Scheller, R.H., Takai, Y. J. Biol. Chem. (1996) [Pubmed]
  12. Identification and characterization of two distinct calmodulin-binding sites in the Trpl ion-channel protein of Drosophila melanogaster. Warr, C.G., Kelly, L.E. Biochem. J. (1996) [Pubmed]
  13. The second PDZ domain of INAD is a type I domain involved in binding to eye protein kinase C. Mutational analysis and naturally occurring variants. Kumar, R., Shieh, B.H. J. Biol. Chem. (2001) [Pubmed]
  14. Scaffolding protein INAD regulates deactivation of vision by promoting phosphorylation of transient receptor potential by eye protein kinase C in Drosophila. Popescu, D.C., Ham, A.J., Shieh, B.H. J. Neurosci. (2006) [Pubmed]
  15. 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]
  16. Reversible phosphorylation of the signal transduction complex in Drosophila photoreceptors. Liu, M., Parker, L.L., Wadzinski, B.E., Shieh, B.H. J. Biol. Chem. (2000) [Pubmed]
  17. Protein kinase C (PKC) isoforms in Drosophila. Shieh, B.H., Parker, L., Popescu, D. J. Biochem. (2002) [Pubmed]
  18. Regulation of Drosophila TRPC channels by protein and lipid interactions. Raghu, P. Semin. Cell Dev. Biol. (2006) [Pubmed]
  19. DWnt4 regulates cell movement and focal adhesion kinase during Drosophila ovarian morphogenesis. Cohen, E.D., Mariol, M.C., Wallace, R.M., Weyers, J., Kamberov, Y.G., Pradel, J., Wilder, E.L. Dev. Cell (2002) [Pubmed]
  20. The tpa-1 gene of Caenorhabditis elegans encodes two proteins similar to Ca(2+)-independent protein kinase Cs: evidence by complete genomic and complementary DNA sequences of the tpa-1 gene. Sano, T., Tabuse, Y., Nishiwaki, K., Miwa, J. J. Mol. Biol. (1995) [Pubmed]
  21. Animal models in the study of protein kinase C isozymes. Choi, D.S., Messing, R.O. Methods Mol. Biol. (2003) [Pubmed]
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