High impact information on ninaA

• We now show that mutations in the ninaA gene severely inhibit opsin transport from the ER, leading to dramatic accumulations of ER cisternae in the photoreceptor cells [1].
• The cyclophilin homolog ninaA is a tissue-specific integral membrane protein required for the proper synthesis of a subset of Drosophila rhodopsins [2].
• 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 [3].
• The ninaA gene was isolated and found to encode a 237-amino-acid protein that has over 40% amino-acid sequence identity with the vertebrate cyclosporin A-binding protein, cyclophilin, a protein that seems to be involved in T-lymphocyte activation [3].
• We find no evidence that the ninaA-encoded protein is directly involved in phototransduction [4].

Biological context of ninaA

• The ninaA gene required for visual transduction in Drosophila encodes a homologue of cyclosporin A-binding protein [3].
• In an attempt to identify mammalian cyclophilins with properties similar to the NinaA protein, a probe derived from the ninaA cDNA was used to screen bovine retina cDNA libraries [5].
• We also expressed ninaA under an inducible promoter and showed that NinaA is required quantitatively for Rh1 biogenesis [6].
• Each of the three ehtyl methanesulfonate-induced ninaA mutant alleles analyzed shows a single nucleotide change in the mRNA coding region leading to either a nonsense or a missense mutation [4].
• Drosophila ninaA gene encodes an eye-specific cyclophilin (cyclosporine A binding protein) [4].

Anatomical context of ninaA

• In ninaA mutants, Rh1 is retained within the endoplasmic reticulum and rhodopsin levels are reduced > 100-fold [6].
• From these results we conclude that the prolyl-cis/trans isomerase activity of the ninaA in the stably transformed Sfn cell line was responsible, directly or indirectly, for the improved folding of the heterologously produced human dopamine transporter [7].

Physical interactions of ninaA

• The ninaA protein is a membrane bound cyclophilin which acts as a peptidyl-prolyl cis/trans isomerase during the folding process of rhodopsin 1 in D. melanogaster rhabdomere [7].

Regulatory relationships of ninaA

• Isolation of the ninaA gene by chromosomal walking revealed that it is expressed only in the eye and encodes a 237-amino acid polypeptide that shows strong sequence similarity to cyclophilin, a putative molecular target for cyclosporine A, a potent immunosuppressant used in human organ transplantations [4].

Other interactions of ninaA

• Mutations in the Drosophila ninaA gene cause dramatic reductions in rhodopsin levels, leading to impaired visual function [2].
• Identification of at least two of the proteins discussed was totally unexpected: the rhodopsin chaperone protein, ninaA, and the signal complex scaffold protein, INAD [8].

Analytical, diagnostic and therapeutic context of ninaA

• Genetic dissection of cyclophilin function. Saturation mutagenesis of the Drosophila cyclophilin homolog ninaA [9].

References