RETINA-SPECIFICALLY EXPRESSED NOVEL SUBTYPES OF BOVINE CYCLOPHILIN

The Drosophila ninaA gene encodes photoreceptor-specific cyclophilin t hought to play a critical role in rhodopsin folding or transport durin g its synthesis or maturation in the most abundant subclass of photore ceptors. Cyclophilins comprise a highly conserved family of proteins w hich are the primary targets of the potent immunosuppressive drug, cyc losporin A (CsA), and which display peptidyl prolyl cis-trans-isomeras e (PPIase) activity. 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 retinal cDNA libraries. The scre en identified two major alternatively spliced forms of cDNA that would encode proteins containing a region of high homology to other cycloph ilins and that are expressed specifically in the retina. These protein s represent a new class of cyclophilins with novel structural features and greatly reduced PPIase and CsA binding activities in comparison t o other known cyclophilins. Tissue in situ hybridization and immunoloc alization of the proteins showed that the RNA and protein products are expressed in photoreceptors as well as other retinal neurons. However , among photoreceptors, the proteins are found predominantly in cones. Thus, mammalian retinas do contain cyclophilins that are retina- spec ifically and photoreceptor class-preferentially expressed. The results suggest that, in cones, the main function of these proteins is, like the NinaA protein, to facilitate proper folding or intracellular trans port of opsins.