QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, November 5, 2008, 28(45):11662-11672; doi:10.1523/JNEUROSCI.4006-08.2008

This Article Full Text Full Text (PDF) Supplemental Data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Dizhoor, A. M. Articles by Fain, G. L. Search for Related Content PubMed PubMed Citation Articles by Dizhoor, A. M. Articles by Fain, G. L.

 Previous Article  |  Next Article 

Neurobiology of Disease
Night Blindness and the Mechanism of Constitutive Signaling of Mutant G90D Rhodopsin

Alexander M. Dizhoor,¹ Michael L. Woodruff,² Elena V. Olshevskaya,¹ Marianne C. Cilluffo,³ M. Carter Cornwall,⁴ Paul A. Sieving,^5,6 and Gordon L. Fain^2,7

¹Hafter Research Laboratories, Pennsylvania College of Optometry, Salus University, Elkins Park, Pennsylvania 19027, ²Department of Physiological Science, University of California, Los Angeles, Los Angeles, California 90095-1606, ³Brain Research Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095-1761, ⁴Department of Physiology and Biophysics, Boston University School of Medicine, Boston, Massachusetts 02118-2526, ⁵National Eye Institute and ⁶National Institute on Deafness and Other Communication Disorders–National Institutes of Health, Bethesda, Maryland 20892, and ⁷Jules Stein Eye Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095-7000

Correspondence should be addressed to Dr. Gordon L. Fain, Department of Physiological Science, University of California, Los Angeles, 3836 Life Sciences, Los Angeles, CA 90095-1606. Email: gfain{at}ucla.edu

The G90D rhodopsin mutation is known to produce congenital night blindness in humans. This mutation produces a similar condition in mice, because rods of animals heterozygous (D+) or homozygous (D+/+) for this mutation have decreased dark current and sensitivity, reduced Ca²⁺, and accelerated values of _REC and _D, similar to light-adapted wild-type (WT) rods. Our experiments indicate that G90D pigment activates the cascade, producing an equivalent background light of 130 Rh* rod^–1 for D+ and 890 Rh* rod^–1 for D+/+. The active species of the G90D pigment could be unregenerated G90D opsin or G90D rhodopsin, either spontaneously activated (as Rh*) or in some other form. Addition of 11-cis-retinal in lipid vesicles, which produces regeneration of both WT and G90D opsin in intact rods and ROS membranes, had no effect on the waveform or sensitivity of dark-adapted G90D responses, indicating that the active species is not G90D opsin. The noise spectra of dark-adapted G90D and WT rods are similar, and the G90D noise variance is much less than of a WT rod exposed to background light of about the same intensity as the G90D equivalent light, indicating that Rh* is not the active species. We hypothesize that G90D rhodopsin undergoes spontaneous changes in molecular conformation which activate the transduction cascade with low gain. Our experiments provide the first indication that a mutant form of the rhodopsin molecule bound to its 11-cis-chromophore can stimulate the visual cascade spontaneously at a rate large enough to produce visual dysfunction.

Key words: photoreceptor; rod; transduction; adaptation; rhodopsin; vision

---

Received Aug. 22, 2008; accepted Sept. 30, 2008.

Correspondence should be addressed to Dr. Gordon L. Fain, Department of Physiological Science, University of California, Los Angeles, 3836 Life Sciences, Los Angeles, CA 90095-1606. Email: gfain{at}ucla.edu

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help