Drosophila ninaA gene encodes an eye-specific cyclophilin (cyclosporine A binding protein).

Schneuwly, Stephan; Shortridge, Randall D.; Larrivee, Denis; Ono, Toshiko; Ozaki, Mamiko; Pak, William L.

doi:10.1073/pnas.86.14.5390

Cited by 181 publications

(131 citation statements)

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“…The translocation of Rh1 from the ER to the rhabdomere depends on a protein related to peptidyl-prolyl cis-trans [57][58][59][60]. NINAA is localized predominately in the ER and colocalizes with Rh1 in secretory vesicles.…”

Section: Maturation Of Rhodopsinmentioning

confidence: 99%

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Phototransduction and retinal degeneration in Drosophila

Wang

Montell

2007

Pflugers Arch - Eur J Physiol

261

303

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Drosophila visual transduction is the fastest known G-protein-coupled signaling cascade and has therefore served as a genetically tractable animal model for characterizing rapid responses to sensory stimulation. Mutations in over 30 genes have been identified, which affect activation, adaptation, or termination of the photoresponse. Based on analyses of these genes, a model for phototransduction has emerged, which involves phosphoinoside signaling and culminates with opening of the TRP and TRPL cation channels. Many of the proteins that function in phototransduction are coupled to the PDZ containing scaffold protein INAD and form a supramolecular signaling complex, the signalplex. Arrestin, TRPL, and Gα q undergo dynamic light-dependent trafficking, and these movements function in long-term adaptation. Other proteins play important roles either in the formation or maturation of rhodopsin, or in regeneration of phosphatidylinositol 4,5-bisphosphate (PIP 2 ), which is required for the photoresponse. Mutation of nearly any gene that functions in the photoresponse results in retinal degeneration. The underlying bases of photoreceptor cell death are diverse and involve mechanisms such as excessive endocytosis of rhodopsin due to stable rhodopsin/arrestin complexes and abnormally low or high levels of Ca 2+ . Drosophila visual transduction appears to have particular relevance to the cascade in the intrinsically photosensitive retinal ganglion cells in mammals, as the photoresponse in these latter cells appears to operate through a remarkably similar mechanism.

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Section: Maturation Of Rhodopsinmentioning

confidence: 99%

“…One chaperone, NINAA, is a cyclophilin-related protein, which is thought to promote the proper folding of Rh1 [57,58,60]. In the absence of NINAA, Rh1 accumulates in the ER and retinal degeneration ensues.…”

Section: Retinal Degenerationmentioning

confidence: 99%

Phototransduction and retinal degeneration in Drosophila

Wang

Montell

2007

Pflugers Arch - Eur J Physiol

261

303

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“…Sequence motifs closely matching the RCS I consensus have been noted (Mismer and Rubin 1989; M. Fortini and C.S. Zuker, unpubl.I in the proximal 5' regions of several Drosophila genes expressed specifically in all or part of the photoreceptor cell population, namely trp (Montell and Rubin 1989;Wong et al 1989), ninaA (Schneuwly et al 1989;Shieh et al 1989), ninaC (Montell and Rubin 1988), chp , and arrestin (Smith et al 1990). RCS I may thus confer on a promoter the ability to be potentially activated in all photoreceptor cells, with more restricted cell-type specificities determined by upstream cis-acting elements.…”

Section: Report) D Virilis Rh3 and Rh4mentioning

confidence: 99%

Analysis of cis-acting requirements of the Rh3 and Rh4 genes reveals a bipartite organization to rhodopsin promoters in Drosophila melanogaster.

Fortini

Rubin²

1990

Genes Dev.

219

162

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The rhodopsin genes of Drosophila melanogaster are expressed in nonoverlapping subsets of photoreceptor cells within the insect visual system. Two of these genes, Rh3 and Rh4, are known to display complementary expression patterns in the UV-sensitive R7 photoreceptor cell population of the compound eye. In addition, we find that Rh3 is expressed in a small group of paired R7 and R8 photoreceptor cells at the dorsal eye margin that are apparently specialized for the detection of polarized light. In this paper we present a detailed characterization of the cis-acting requirements of both Rh3 and Rh4. Promoter deletion series demonstrate that small regulatory regions (<300 bp) of both R7 opsin genes contain DNA sequences sufficient to generate their respective expression patterns. Individual cis-acting elements were further identified by oligonucleotidedirected mutagenesis guided by interspecific sequence comparisons. Our results suggest that the Drosophila rhodopsin genes share a simple bipartite promoter structure, whereby the proximal region constitutes a functionally equivalent promoter "core" and the distal region determines cell-type specificity. The expression patterns of several hybrid rhodopsin promoters, in which all or part of the putative core regions have been replaced with the analogous regions of different rhodopsin promoters, provide additional evidence in support of this model.

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“…In metazoans this may not necessarily be the case, and there are several examples where secreted CYPs are involved in distinct functions. The best characterized example is the specific folding of the photoreceptor rhodopsin by the ninaA cyclophilin in Drosophila melonogaster (6,7). In addition, the secreted vertebrate cyclophilin B isoform has been established as assisting the proper folding and exit of type I procollagen from the ER (27).…”

Section: Discussionmentioning

confidence: 99%

“…The major exception to the lack of associated phenotype for an immunophilin mutant has been described for the ninaA cyclophilin gene of Drosophila. This gene product is involved in rhodopsin folding, and mutant forms result in protein misfolding leading to blindness (6,7).…”

mentioning

confidence: 99%

Loss of Secretory Pathway FK506-binding Proteins Results in Cold-sensitive Lethality and Associate Extracellular Matrix Defects in the Nematode Caenorhabditis elegans

Winter

Eschenlauer

McCormack

et al. 2007

Journal of Biological Chemistry

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The FK506-binding proteins (FKBs) represent ubiquitous enzymes that catalyze the rate-limiting peptidyl prolyl cis-trans isomerization step in protein folding. The nematode Caenorhabditis elegans has eight FKBs, three of which (FKB-3, -4, and -5) have dual peptidyl prolyl cis-trans isomerase (PPIase) domains, signal peptides and ER retention signals. PPIase activity has been detected for recombinant FKB-3. Both FKB-3 and -5 are expressed in the exoskeleton-synthesizing hypodermis with transcript peaks that correspond to the molting and collagen synthesis cycles. FKB-4 is expressed at a low level throughout development. No phenotypes were observed in deletion mutants in each of the secretory pathway FKBs. Combined triple and fkb-4, -5 double deletion mutants were however found to arrest at 12°C, but developed normally at 15-25°C. This coldsensitive larval lethal effect was not maternally derived, occurred during embryogenesis, and could be rescued following the transgenic introduction of a wild type copy of either fkb-4 or fkb-5. The temperature-sensitive defects also affected molting, cuticle collagen expression, hypodermal seam cell morphology, and the structural integrity of the cuticular extracellular matrix. This study establishes that the secretory pathway FK506-binding PPIase enzymes are essential for normal nematode development, collagen biogenesis, and the formation of an intact exoskeleton under adverse physiological conditions. The FK506-binding proteins (FKBPs or FKBs)2 belong to a group of proteins that have peptidyl prolyl cis-trans isomerase (PPIase, EC 5.2.1.8) activity, and together with the cyclophilins (CYPs or CYNs) are collectively called the immunophilins. FKBs and CYPs are structurally unrelated and have high affinities for the structurally distinct immunosuppressive drugs FK506 and cyclosporin A, respectively (1). In addition, there is no link between PPIase activity and the immunosuppressive action of these compounds. The immunophilins have a widespread distribution in nature being found in bacteria, plants, and man. However, the endogenous physiological functions are poorly understood but include possible roles in protein translation, folding, assembly, and trafficking (1, 2). These enzymes stabilize the cis-trans transition state, accelerate the isomerization event and therefore promote protein folding and assembly of multiprotein complexes.The collective roles of the FKBs and CYPs have been addressed following the generation of single and multiple mutants in the budding yeast Saccharomyces cerevisiae. No overt phenotypes were observed, indicating that they are dispensable for normal development in this simple unicellular organism (3). The examination of immunophilin function in multicellular organisms has likewise been relatively uninformative raising the possibility of redundancy of function and the possible non-essential nature of these genes. In relation to PPIase activity, this is supported by the fact that proline isomerization will proceed in the absence of a PPIase catalyst, alb...

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Drosophila ninaA gene encodes an eye-specific cyclophilin (cyclosporine A binding protein).

Cited by 181 publications

References 30 publications

Phototransduction and retinal degeneration in Drosophila

Phototransduction and retinal degeneration in Drosophila

Analysis of cis-acting requirements of the Rh3 and Rh4 genes reveals a bipartite organization to rhodopsin promoters in Drosophila melanogaster.

Loss of Secretory Pathway FK506-binding Proteins Results in Cold-sensitive Lethality and Associate Extracellular Matrix Defects in the Nematode Caenorhabditis elegans

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