Enhanced shutoff of phototransduction in transgenic mice expressing palmitoylation-deficient rhodopsin.
Palmitoylation is a reversible, post-translational modification observed in a number of G-protein-coupled receptors. To gain a better understanding of its role in visual transduction, we produced transgenic knock-in mice that expressed a palmitoylation-deficient rhodopsin (Palm(-/-)). The mutant rhodopsin was expressed at wild-type levels and showed normal cellular localization to rod outer segments, indicating that neither rhodopsin stability nor its intracellular trafficking were compromised. But Palm(-/-) rods had briefer flash responses and reduced sensitivity to flashes and to steps of light. Upon exposure to light, rhodopsin became phosphorylated at a faster rate in mutant than in wild-type retinas. Since quench of rhodopsin begins with its phosphorylation, these results suggest that palmitoylation may modulate rod photoreceptor sensitivity by permitting rhodopsin to remain active for a longer period.
Wang
Zhongyan
Z
Molecular Cardiology Research Institute, Tufts-New England Medical Center, Boston, Massachusetts 02111, USA.
Wen
Xiao-Hong
XH
Ablonczy
Zsolt
Z
Crouch
Rosalie K
RK
Makino
Clint L
CL
Lem
Janis
J
D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D003545:Cysteine / Q000737:chemistry; D004566:Electrodes; D015723:Gene Library; D007150:Immunohistochemistry; D008027:Light; D013058:Mass Spectrometry; D051379:Mice; D008822:Mice, Transgenic; D008957:Models, Genetic; D015233:Models, Statistical; D008969:Molecular Sequence Data; D009154:Mutation; D019308:Palmitic Acid / Q000737:chemistry; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D012313:RNA / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000737:chemistry; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000502:physiology; D012160:Retina / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012243:Rhodopsin / Q000737:chemistry / Q000235:genetics*; D013997:Time Factors
D017382:Reactive Oxygen Species; D043562:Receptors, G-Protein-Coupled; D019308:Palmitic Acid; D012313:RNA; D012243:Rhodopsin; D003545:Cysteine