The cyclophilin homolog ninaA is required in the secretory pathway.
In Drosophila, the major rhodopsin Rh1 is synthesized in endoplasmic reticulum (ER)-bound ribosomes of the R1-R6 photoreceptor cells and is then transported to the rhabdomeres where it functions in phototransduction. Mutations in the cyclophilin homolog ninaA lead to a 90% reduction in Rh1 opsin. Cyclophilins have been shown to be peptidyl-prolyl cis-trans isomerases and have been implicated in catalyzing protein folding. 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. These results demonstrate that ninaA functions in the ER. Interestingly, ninaA and Rh1 also colocalize to secretory vesicles, suggesting that Rh1 may require ninaA as it travels through the distal compartments of the secretory pathway. These results are discussed in relation to the possible role of cyclophilins in protein folding and intracellular protein trafficking.
Colley
N J
NJ
Howard Hughes Medical Institute University of California, San Diego, La Jolla 92093.
Baker
E K
EK
Stamnes
M A
MA
Zuker
C S
CS
D000591:Amino Acid Isomerases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D004553:Electric Conductivity; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D007150:Immunohistochemistry; D007301:Insect Hormones / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D016253:Microscopy, Immunoelectron; D018832:Molecular Chaperones; D009154:Mutation / Q000235:genetics; D019696:Peptidylprolyl Isomerase; D010775:Photic Stimulation; D010786:Photoreceptor Cells / Q000378:metabolism; D011487:Protein Conformation; D012243:Rhodopsin / Q000235:genetics / Q000378:metabolism*
D002352:Carrier Proteins; D029721:Drosophila Proteins; D007301:Insect Hormones; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; C068480:ninaA protein, Drosophila; D012243:Rhodopsin; D000591:Amino Acid Isomerases; D019696:Peptidylprolyl Isomerase