Files and links (2)
Published, Version of Record (VoR)Open Access (License Unspecified), Open
Journal article
Night Blindness and the Mechanism of Constitutive Signaling of Mutant G90D Rhodopsin
The Journal of neuroscience, v 28(45), pp 11662-11672
05 Nov 2008
PMID: 18987202
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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 tau(REC) and tau(D), similar to light-adapted wild-type (WT) rods. Our experiments indicate that G90D pigment activates the cascade, producing an equivalent background light of similar to 130 Rh-star rod(-1) for D+ and 890 Rh-star rod(-1) for D+/+. The active species of the G90D pigment could be unregenerated G90D opsin or G90D rhodopsin, either spontaneously activated (as Rh-star) 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-star 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.
Metrics
Details
- Title
- Night Blindness and the Mechanism of Constitutive Signaling of Mutant G90D Rhodopsin
- Creators
- Alexander M. Dizhoor - Salus UniversityMichael L. Woodruff - University of California, Los AngelesElena V. Olshevskaya - Salus UniversityMarianne C. Cilluffo - University of California, Los AngelesM. Carter Cornwall - Boston UniversityPaul A. Sieving - National Institutes of HealthGordon L. Fain - University of California, Los Angeles
- Publication Details
- The Journal of neuroscience, v 28(45), pp 11662-11672
- Publisher
- Soc Neuroscience
- Number of pages
- 11
- Grant note
- Pennsylvania Lions Sight Preservation Foundation UCLA; University of California System National Eye Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Eye Institute (NEI) EY11522; EY01157; EY01844; EY 00331 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA National Institute on Deafness and Other Communication Disorders Intramural; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Deafness & Other Communication Disorders (NIDCD)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy; Pennsylvania College of Optometry (PCO)
- Web of Science ID
- WOS:000260665900024
- Scopus ID
- 2-s2.0-58149267461
- Other Identifier
- 991022035259704721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Neurosciences