title: Cyclophilin-related protein RanBP2 acts as chaperone for red/green opsin.
abstract: Cyclophilins are ubiquitous and abundant proteins that exhibit peptidyl prolyl cis-trans isomerization (PPlase) activity in vitro. Their functions in vivo, however, are not well understood. Two new retinal cyclophilin isoforms, types I and II, are highly expressed in cone photoreceptors of the vertebrate retina. Type-II cyclophilin is identical to RanBP2, a large protein that binds the GTPase Ran. Here we report that two contiguous domains in RanBP2, Ran-binding domain 4 (RBD4) and cyclophilin, act in concert as a chaperone for the opsin molecule of the red/green-sensitive visual pigment of a dichromatic vertebrate. In Drosophila, the cyclophilin NinaA is expressed in all photoreceptors and is required for the expression of only a subset of opsins. The molecular basis of these photoreceptor class-specific effects and the functions of NinaA and other cyclophilins in vivo remain unclear. Unlike NinaA, which forms a stable complex with opsin from retinular cells R1-6, we find that the cyclophilin domain of RanBP2 does not bind opsin directly; rather, it augments and stabilizes the interaction between red/green (R/G) opsin and the RBD4 domain. This involves a cyclophilin-mediated modification of R/G opsin, possibly involving proline isomerization. The RBD4-cyclophilin supradomain of RanBP2, therefore, is a form of vertebrate chaperone of defined substrate specificity, which may be involved in the processing and/or transport of long-wavelength opsin in cone photoreceptor cells.
authors.affiliation: Department of Psychiatry and Program in Neuroscience, University of Texas Southwestern Medical Center, Dallas 75235-9111, USA.
authors.forename: P A
authors.initials: PA
authors.lastname: Ferreira
authors.forename: T A
authors.initials: TA
authors.lastname: Nakayama
authors.forename: W L
authors.initials: WL
authors.lastname: Pak
authors.forename: G H
authors.initials: GH
authors.lastname: Travis
mesh_terms: D000591:Amino Acid Isomerases / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002352:Carrier Proteins / Q000378:metabolism*; D002417:Cattle; D018833:Chaperonins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004330:Drosophila; D006801:Humans; D018832:Molecular Chaperones; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins / Q000378:metabolism*; D019696:Peptidylprolyl Isomerase; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012160:Retina / Q000378:metabolism; D017299:Rod Opsins / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D018832:Molecular Chaperones; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D017299:Rod Opsins; C095855:long-wavelength opsin; C095854:middle-wavelength opsin; C094493:ran-binding protein 2; D018833:Chaperonins; D000591:Amino Acid Isomerases; D019696:Peptidylprolyl Isomerase