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J. Biol. Chem., Vol. 280, Issue 26, 24293-24300, July 1, 2005

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Enhanced Shutoff of Phototransduction in Transgenic Mice Expressing Palmitoylation-deficient Rhodopsin^*

Zhongyan Wang, Xiao-Hong Wen¶, Zsolt Ablonczy||, Rosalie K. Crouch||, Clint L. Makino¶, and Janis Lem**

From the Molecular Cardiology Research Institute, Tufts-New England Medical Center, Boston, Massachusetts 02111, the ^¶Department of Ophthalmology, Harvard Medical School and Massachusetts Eye and Ear Infirmary, Boston, Massachusetts 02114, the ^||Department of Ophthalmology, Medical University of South Carolina, Charleston, South Carolina 29425, and the ^**Department of Ophthalmology, Program in Genetics, Tufts Center for Vision Research, Tufts University School of Medicine, Boston, Massachusetts 02111

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.

Received for publication, March 8, 2005 , and in revised form, April 20, 2005.

^* This work was supported by Research to Prevent Blindness (Medical University of South Carolina) and by National Institutes of Health (NIH) Grants F2EY13912A (to Z. W.), EY12008 (to J. L.), EY11358 (to C. L. M.), EY04939 (to R. K. C.), EY014799 (to Z. A.), and NIH P30 EY13078 Core Grant for Vision Research awarded to Tufts-New England Medical Center and NIH P30 EY14104 Core Grant for Vision Research awarded to Massachusetts Eye and Ear Infirmary. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

This article was selected as a Paper of the Week.

These authors contributed equally to this work.

To whom correspondence should be addressed: Tufts-New England Medical Center, 750 Washington St., Box 5045, Boston, MA 02111. Tel.: 617-636-5045; Fax: 617-636-8362; E-mail: Jlem{at}Tufts-NEMC.org.

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