Gene Symbol: ninaA
Description: neither inactivation nor afterpotential A
Alias: CG3966, Dmel\CG3966, NINAA, NinaA, ninA, neither inactivation nor afterpotential A, CG3966-PA, either inactivation nor afterpotential A, neither inactivation nor after potential, ninaA-PA
Species: fruit fly

Top Publications

  1. Schneuwly S, Shortridge R, Larrivee D, Ono T, Ozaki M, Pak W. Drosophila ninaA gene encodes an eye-specific cyclophilin (cyclosporine A binding protein). Proc Natl Acad Sci U S A. 1989;86:5390-4 pubmed
    Mutations in the ninaA gene of Drosophila severely reduce the amount of rhodopsin specifically in R1-6 photoreceptors...
  2. Rosenbaum E, Hardie R, Colley N. Calnexin is essential for rhodopsin maturation, Ca2+ regulation, and photoreceptor cell survival. Neuron. 2006;49:229-41 pubmed
    ..Our results illustrate a critical role for calnexin in Rh1 maturation and Ca2+ regulation and provide genetic evidence that defects in calnexin lead to retinal degeneration. ..
  3. Tsunoda S, Sierralta J, Sun Y, Bodner R, Suzuki E, Becker A, et al. A multivalent PDZ-domain protein assembles signalling complexes in a G-protein-coupled cascade. Nature. 1997;388:243-9 pubmed
    ..A picture emerges of a highly organized unit of signalling, a 'transduclisome', with PDZ domains functioning as key elements in the organization of transduction complexes in vivo. ..
  4. Baker E, Colley N, Zuker C. The cyclophilin homolog NinaA functions as a chaperone, forming a stable complex in vivo with its protein target rhodopsin. EMBO J. 1994;13:4886-95 pubmed
    ..biogenesis of the major rhodopsin, Rh1, is dependent on the presence of a photoreceptor cell-specific cyclophilin, NinaA. In ninaA mutants, Rh1 is retained within the endoplasmic reticulum and rhodopsin levels are reduced > 100-fold...
  5. Shieh B, Stamnes M, Seavello S, Harris G, Zuker C. The ninaA gene required for visual transduction in Drosophila encodes a homologue of cyclosporin A-binding protein. Nature. 1989;338:67-70 pubmed
    Mutations of the Drosophila melanogaster ninaA gene affect phototransduction: ninaA mutant flies have a 10-fold reduction in the levels of rhodopsin in the R1-R6 photoreceptor cells...
  6. Larrivee D, Conrad S, Stephenson R, Pak W. Mutation that selectively affects rhodopsin concentration in the peripheral photoreceptors of Drosophila melanogaster. J Gen Physiol. 1981;78:521-45 pubmed
    ..The results suggest that the mutation affects the opsin, rather than the chromophore, component of rhodopsin molecules in the R1-6 photoreceptors. The interaction between the chromophore and R1-6 opsin, however, appears to be normal. ..
  7. Colley N, Baker E, Stamnes M, Zuker C. The cyclophilin homolog ninaA is required in the secretory pathway. Cell. 1991;67:255-63 pubmed
    ..Mutations in the cyclophilin homolog ninaA lead to a 90% reduction in Rh1 opsin...
  8. Mendes C, Levet C, Chatelain G, Dourlen P, Fouillet A, Dichtel Danjoy M, et al. ER stress protects from retinal degeneration. EMBO J. 2009;28:1296-307 pubmed publisher
    ..Here, we found that mutations in the ER-resident chaperone, neither inactivation nor afterpotential A (NinaA), lead to mild ER stress, protecting photoreceptor neurons from various death stimuli in ..
  9. Webel R, Menon I, O Tousa J, Colley N. Role of asparagine-linked oligosaccharides in rhodopsin maturation and association with its molecular chaperone, NinaA. J Biol Chem. 2000;275:24752-9 pubmed
    ..most abundant rhodopsin, is glycosylated in the endoplasmic reticulum (ER) and requires its molecular chaperone, NinaA, for exit from the ER and transport through the secretory pathway...

More Information


  1. Kurada P, O Tousa J. Retinal degeneration caused by dominant rhodopsin mutations in Drosophila. Neuron. 1995;14:571-9 pubmed
    ..A posttranslational event subsequent to the requirement for the ninaA-encoded cyclophilin is disrupted by the dominant mutations...
  2. Stamnes M, Shieh B, Chuman L, Harris G, Zuker C. The cyclophilin homolog ninaA is a tissue-specific integral membrane protein required for the proper synthesis of a subset of Drosophila rhodopsins. Cell. 1991;65:219-27 pubmed
    Mutations in the Drosophila ninaA gene cause dramatic reductions in rhodopsin levels, leading to impaired visual function. The ninaA protein is a homolog of peptidyl-prolyl cis-trans isomerases...
  3. Zuker C. The biology of vision of Drosophila. Proc Natl Acad Sci U S A. 1996;93:571-6 pubmed
    ..In this manuscript I review some of our recent findings and the strategies used to dissect this process. ..
  4. Rosenbaum E, Brehm K, Vasiljevic E, Liu C, Hardie R, Colley N. XPORT-dependent transport of TRP and rhodopsin. Neuron. 2011;72:602-15 pubmed publisher
    ..Our results identify XPORT as a molecular chaperone and provide a mechanistic link between TRP channels and their GPCRs during biosynthesis and transport. ..
  5. Ahmad S, Natochin M, Barren B, Artemyev N, O Tousa J. Heterologous expression of bovine rhodopsin in Drosophila photoreceptor cells. Invest Ophthalmol Vis Sci. 2006;47:3722-8 pubmed
    ..The system allows the characterization and comparison of vertebrate and invertebrate visual pigment properties in a common cell type. ..
  6. Xu Z, Chikka M, Xia H, Ready D. Ire1 supports normal ER differentiation in developing Drosophila photoreceptors. J Cell Sci. 2016;129:921-9 pubmed publisher
    ..Instead, ER proliferates in persistent and ribosome-poor tubular tangles. A phase of Ire1 activity early in R cell development thus shapes dynamic ER. ..
  7. Fortini M, Bonini N. Modeling human neurodegenerative diseases in Drosophila: on a wing and a prayer. Trends Genet. 2000;16:161-7 pubmed
    ..With the advent of complete genomic sequencing on the horizon, Drosophila will continue to be an outstanding model system in which to unravel the complexities, causes and treatments for human neural degeneration. ..
  8. Ranganathan R, Harris W, Zuker C. The molecular genetics of invertebrate phototransduction. Trends Neurosci. 1991;14:486-93 pubmed
    ..The results of a combination of molecular, genetic, physiological and biochemical studies are beginning to produce a clearer model for the complex mechanisms involved in invertebrate visual transduction. ..
  9. Rosenbaum E, Vasiljevic E, Brehm K, Colley N. Mutations in four glycosyl hydrolases reveal a highly coordinated pathway for rhodopsin biosynthesis and N-glycan trimming in Drosophila melanogaster. PLoS Genet. 2014;10:e1004349 pubmed publisher
  10. Tian Y, Li T, Sun M, Wan D, Li Q, Li P, et al. Neurexin regulates visual function via mediating retinoid transport to promote rhodopsin maturation. Neuron. 2013;77:311-22 pubmed publisher
    ..Our results reveal a role for Neurexin in mediating retinoid transport and subsequent rhodopsin maturation and suggest that Neurexin regulates lipoprotein function. ..
  11. Satoh T, Ohba A, Liu Z, Inagaki T, Satoh A. dPob/EMC is essential for biosynthesis of rhodopsin and other multi-pass membrane proteins in Drosophila photoreceptors. elife. 2015;4: pubmed publisher
    ..essential for stabilization of immature Rh1 in an earlier step than that at which another Rh1-specific chaperone (NinaA) acts. dPob/EMC3 localizes to the ER and associates with EMC1 and calnexin...
  12. Bentrop J, Schwab K, Pak W, Paulsen R. Site-directed mutagenesis of highly conserved amino acids in the first cytoplasmic loop of Drosophila Rh1 opsin blocks rhodopsin synthesis in the nascent state. EMBO J. 1997;16:1600-9 pubmed
    ..Photoreceptor cells expressing mutant rhodopsins undergo age-dependent degeneration in a recessive manner. ..
  13. Pak W. Drosophila in vision research. The Friedenwald Lecture. Invest Ophthalmol Vis Sci. 1995;36:2340-57 pubmed
    ..The identification of the NinaA protein and its role as chaperon and/or foldase for opsin would not have been possible without the genetic ..
  14. Kurada P, Tonini T, Serikaku M, Piccini J, O Tousa J. Rhodopsin maturation antagonized by dominant rhodopsin mutants. Vis Neurosci. 1998;15:693-700 pubmed
    ..These results are consistent with the view that the ninaE(D1) rhodopsin antagonizes an early posttranslation process that is specific for maturation of the ninaE-encoded rhodopsin. ..
  15. Selinger Z, Doza Y, Minke B. Mechanisms and genetics of photoreceptors desensitization in Drosophila flies. Biochim Biophys Acta. 1993;1179:283-99 pubmed
  16. Landry C, Castillo Davis C, Ogura A, Liu J, Hartl D. Systems-level analysis and evolution of the phototransduction network in Drosophila. Proc Natl Acad Sci U S A. 2007;104:3283-8 pubmed
    ..These results provide a preliminary quantification of variation and divergence of gene expression between species in a known gene network and provide a foundation for a system-level understanding of functional and evolutionary change. ..
  17. Gu G, Yang J, Mitchell K, O Tousa J. Drosophila ninaB and ninaD act outside of retina to produce rhodopsin chromophore. J Biol Chem. 2004;279:18608-13 pubmed
    ..Retinal or another C(20) retinoid, not members of the beta-carotene family of C(40) carotenoids, are supplied to photoreceptors for rhodopsin biogenesis. ..
  18. Rosenbaum E, Vasiljevic E, Cleland S, Flores C, Colley N. The Gos28 SNARE protein mediates intra-Golgi transport of rhodopsin and is required for photoreceptor survival. J Biol Chem. 2014;289:32392-409 pubmed publisher
    ..Our results identify Gos28 as an essential SNARE protein in Drosophila photoreceptors and provide mechanistic insights into the role of SNAREs in neurodegenerative disease. ..
  19. Edwin Chan H, Harris S, O Kane C. Identification and characterization of kraken, a gene encoding a putative hydrolytic enzyme in Drosophila melanogaster. Gene. 1998;222:195-201 pubmed
    ..We suggest a role for Kraken in detoxification and digestion during embryogenesis and larval development. ..
  20. Zuker C. Phototransduction in Drosophila: a paradigm for the genetic dissection of sensory transduction cascades. Curr Opin Neurobiol. 1992;2:622-7 pubmed
    ..The availability of Drosophila mutants with defects in visual physiology allows for an in vivo dissection of this complex sensory signal transduction process. ..
  21. Alvarez C, Robison K, Gilbert W. Novel Gq alpha isoform is a candidate transducer of rhodopsin signaling in a Drosophila testes-autonomous pacemaker. Proc Natl Acad Sci U S A. 1996;93:12278-82 pubmed
    ..This proposal is supported by the finding that rhodopsin 2 and arrestin 1, two photoreceptor-cell-specific genes, are also expressed in male gonads. ..
  22. Kunduri G, Yuan C, Parthibane V, Nyswaner K, Kanwar R, Nagashima K, et al. Phosphatidic acid phospholipase A1 mediates ER-Golgi transit of a family of G protein-coupled receptors. J Cell Biol. 2014;206:79-95 pubmed publisher
    ..Our findings show that a cytosolic protein is necessary for transit of selective transmembrane receptor cargo by the COPII coat for anterograde trafficking. ..
  23. Stephenson R, O TOUSA J, Scavarda N, Randall L, Pak W. Drosophila mutants with reduced rhodopsin content. Symp Soc Exp Biol. 1983;36:477-501 pubmed
  24. Fouillet A, Levet C, Virgone A, Robin M, Dourlen P, Rieusset J, et al. ER stress inhibits neuronal death by promoting autophagy. Autophagy. 2012;8:915-26 pubmed publisher
    ..Based on our findings, we conclude that autophagy is required for the neuroprotection mediated by mild ER stress, and therefore ER preconditioning has potential therapeutic value for the treatment of neurodegenerative diseases. ..
  25. Satoh A, Xia H, Yan L, Liu C, Hardie R, Ready D. Arrestin translocation is stoichiometric to rhodopsin isomerization and accelerated by phototransduction in Drosophila photoreceptors. Neuron. 2010;67:997-1008 pubmed publisher
    ..Our results indicate that Arr2 translocation in Drosophila photoreceptors is driven by diffusion, but profoundly accelerated by phototransduction and Ca2+ influx. ..
  26. Mitra A, Chinchore Y, Kinser R, Dolph P. Characterization of two dominant alleles of the major rhodopsin-encoding gene ninaE in Drosophila. Mol Vis. 2011;17:3224-33 pubmed
    ..Confocal microscopy was performed on dissected retinas stained with antibodies specific for rhodopsin, NinaA, and F-actin. Rhodopsin levels were determined by western and slot blot analysis...
  27. Chen Z, Chen H, Montell C. TRP and Rhodopsin Transport Depends on Dual XPORT ER Chaperones Encoded by an Operon. Cell Rep. 2015;13:573-584 pubmed publisher
    ..Our work highlights a coordinated network of chaperones required for the biosynthesis of the TRP channel and rhodopsin in Drosophila photoreceptor cells. ..
  28. Lenhard T, Reiländer H. Engineering the folding pathway of insect cells: generation of a stably transformed insect cell line showing improved folding of a recombinant membrane protein. Biochem Biophys Res Commun. 1997;238:823-30 pubmed
    ..Here, we report the construction of a Sf9 insect cell line stably transformed with the ninaA gene from D. melanogaster (Sfn cell line)...
  29. Zemelman B, Lee G, Ng M, Miesenbock G. Selective photostimulation of genetically chARGed neurons. Neuron. 2002;33:15-22 pubmed
    ..Distributed activity may thus be fed directly into a circumscribed population of neurons in intact tissue, irrespective of the spatial arrangement of its elements. ..
  30. Dolph P, Ranganathan R, Colley N, Hardy R, Socolich M, Zuker C. Arrestin function in inactivation of G protein-coupled receptor rhodopsin in vivo. Science. 1993;260:1910-6 pubmed
    ..These results demonstrate the fundamental requirement for members of the arrestin protein family in the regulation of G protein-coupled receptors and signaling cascades in vivo. ..
  31. Hemenway C, Heitman J. Proline isomerases in microorganisms and small eukaryotes. Ann N Y Acad Sci. 1993;696:38-46 pubmed
  32. Pak W, Conrad S, Kremer N, Larrivee D, Schinz R, Wong F. Photoreceptor function. Basic Life Sci. 1980;16:331-46 pubmed
  33. Ondek B, Hardy R, Baker E, Stamnes M, Shieh B, Zuker C. Genetic dissection of cyclophilin function. Saturation mutagenesis of the Drosophila cyclophilin homolog ninaA. J Biol Chem. 1992;267:16460-6 pubmed
    ..The Drosophila ninaA gene encodes a photoreceptor-specific cyclophilin homolog involved in rhodopsin biogenesis...
  34. Zuker C, Mismer D, Hardy R, Rubin G. Ectopic expression of a minor Drosophila opsin in the major photoreceptor cell class: distinguishing the role of primary receptor and cellular context. Cell. 1988;53:475-82 pubmed
    ..In addition, we show that two mutants that specifically affect the R1-R6 cells, ninaA and rdgB, do not directly affect expression of the ninaE gene.
  35. Smith D, Shieh B, Zuker C. Isolation and structure of an arrestin gene from Drosophila. Proc Natl Acad Sci U S A. 1990;87:1003-7 pubmed
    ..However, the arrestin gene does not appear to be the ninaD locus, as sequence analysis of three ethylmethane sulfate-induced ninaD mutant alleles reveals no alteration in amino acid sequence. ..
  36. Huang Y, Xie J, Wang T. A Fluorescence-Based Genetic Screen to Study Retinal Degeneration in Drosophila. PLoS ONE. 2015;10:e0144925 pubmed publisher
    ..Our findings demonstrate that this "Rh1::GFP ey-flp/hid" method enables high-throughput F1 genetic screens to rapidly and precisely identify mutations of retinal degeneration. ..
  37. Ozaki K, Nagatani H, Ozaki M, Tokunaga F. Maturation of major Drosophila rhodopsin, ninaE, requires chromophore 3-hydroxyretinal. Neuron. 1993;10:1113-9 pubmed
    ..Based on these results, we present a novel mechanism of protein regulatory expression; that is, chromophore posttranslationally controls the expression of apoprotein by promoting its maturation. ..
  38. Park S, Ludwig M, Tamarina N, He B, Carl S, Dickerson D, et al. Genetic complexity in a Drosophila model of diabetes-associated misfolded human proinsulin. Genetics. 2014;196:539-55 pubmed publisher
    ..The genetic dominance of disease-specific phenotypic variability in our model of misfolded human proinsulin makes this approach amenable to genome-wide association study in a simple F1 screen of natural variation. ..
  39. Vosshall L, Young M. Circadian rhythms in Drosophila can be driven by period expression in a restricted group of central brain cells. Neuron. 1995;15:345-60 pubmed
    ..When we genetically removed all external photoreceptor cells, rhythms persisted in these transgenic animals. This suggests that a few central brain cells producing glass and per are capable of generating biological rhythms. ..