11-cis-retinal reduces constitutive opsin phosphorylation and improves quantum catch in retinoid-deficient mouse rod photoreceptors.
Rpe65(-/-) mice produce minimal amounts of 11-cis-retinal, the ligand necessary for the formation of photosensitive visual pigments. Therefore, the apoprotein opsin in these animals has not been exposed to its normal ligand. The Rpe65(-/-) mice contain less than 0.1% of wild type levels of rhodopsin. Mass spectrometric analysis of opsin from Rpe65(-/-) mice revealed unusually high levels of phosphorylation in dark-adapted mice but no other structural alterations. Single flash and flicker electroretinograms (ERGs) from 1-month-old animals showed trace rod function but no cone response. B-wave kinetics of the single-flash ERG are comparable with those of dark-adapted wild type mice containing a full compliment of rhodopsin. Application (intraperitoneal injection) of 11-cis-retinal to Rpe65(-/-) mice increased the rod ERG signal, increased levels of rhodopsin, and decreased opsin phosphorylation. Therefore, exogenous 11-cis-retinal improves photoreceptor function by regenerating rhodopsin and removes constitutive opsin phosphorylation. Our results indicate that opsin, which has not been exposed to 11-cis-retinal, does not generate the activity generally associated with the bleached apoprotein.
Ablonczy
Zsolt
Z
Department of Ophthalmology, Medical University of South Carolina, 167 Ashley Avenue, Charleston, SC 29425, USA.
Crouch
Rosalie K
RK
Goletz
Patrice W
PW
Redmond
T Michael
TM
Knapp
Daniel R
DR
Ma
Jian-Xing
JX
Rohrer
Barbel
B
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins; D005136:Eye Proteins; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism*; D012172:Retinaldehyde / Q000494:pharmacology*; D017299:Rod Opsins / Q000737:chemistry / Q000378:metabolism*; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
D002352:Carrier Proteins; D005136:Eye Proteins; D011506:Proteins; D012172:Retinaldehyde; D017299:Rod Opsins; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase