Molecular Genetics of Inherited Variation in Human Color Vision

Nathans, Jeremy; Piantanida, Thomas P.; Eddy, Roger L.; Shows, Thomas B.; Hogness, David S.

doi:10.1126/science.3485310

Cited by 700 publications

(389 citation statements)

References 15 publications

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“…This very high sequence identity has prompted the assumption that both green and red pigments share the same structural and functional features. The blue pigment, however, shows a lower degree of 43 % homology to the red and green opsins [ 5 ]. Thus, aside from their specific role in spectral tuning into different absorption wavelengths, the differences in structurefunction relationships caused by this minor sequence variance have not been previously elucidated.…”

Section: Electronic Supplementary Materialsmentioning

confidence: 99%

Beyond spectral tuning: human cone visual pigments adopt different transient conformations for chromophore regeneration

Srinivasan

Cordomí

Ramon

et al. 2015

Cell. Mol. Life Sci.

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Human red and green visual pigments are seven transmembrane receptors of cone photoreceptor cells of the retina that mediate color vision. These pigments share a very high degree of homology and have been assumed to feature analogous structural and functional properties. We report on a different regeneration mechanism among red and green cone opsins with retinal analogs using UV-Vis/fluorescence spectroscopic analyses, molecular modeling and site-directed mutagenesis. We find that photoactivated green cone opsin adopts a transient conformation which regenerates via an unprotonated Schiff base linkage with its natural chromophore, whereas red cone opsin forms a typical protonated Schiff base. The chromophore regeneration kinetics is consistent with a secondary retinal uptake by the cone pigments. Overall, our findings reveal, for the

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Section: Electronic Supplementary Materialsmentioning

confidence: 99%

Beyond spectral tuning: human cone visual pigments adopt different transient conformations for chromophore regeneration

Srinivasan

Cordomí

Ramon

et al. 2015

Cell. Mol. Life Sci.

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“…This observation turned out to have relevance to human retinal dystrophies, as mutations in human rhodopsin were shown subsequently to account for a large proportion of the cases of autosomal dominant retinitis pigmentosa disease (ADRP) [209][210][211][212][213].…”

Section: Retinal Degenerationmentioning

confidence: 99%

Phototransduction and retinal degeneration in Drosophila

Wang

Montell

2007

Pflugers Arch - Eur J Physiol

257

303

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Drosophila visual transduction is the fastest known G-protein-coupled signaling cascade and has therefore served as a genetically tractable animal model for characterizing rapid responses to sensory stimulation. Mutations in over 30 genes have been identified, which affect activation, adaptation, or termination of the photoresponse. Based on analyses of these genes, a model for phototransduction has emerged, which involves phosphoinoside signaling and culminates with opening of the TRP and TRPL cation channels. Many of the proteins that function in phototransduction are coupled to the PDZ containing scaffold protein INAD and form a supramolecular signaling complex, the signalplex. Arrestin, TRPL, and Gα q undergo dynamic light-dependent trafficking, and these movements function in long-term adaptation. Other proteins play important roles either in the formation or maturation of rhodopsin, or in regeneration of phosphatidylinositol 4,5-bisphosphate (PIP 2 ), which is required for the photoresponse. Mutation of nearly any gene that functions in the photoresponse results in retinal degeneration. The underlying bases of photoreceptor cell death are diverse and involve mechanisms such as excessive endocytosis of rhodopsin due to stable rhodopsin/arrestin complexes and abnormally low or high levels of Ca 2+ . Drosophila visual transduction appears to have particular relevance to the cascade in the intrinsically photosensitive retinal ganglion cells in mammals, as the photoresponse in these latter cells appears to operate through a remarkably similar mechanism.

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“…22 This may result in the deletion of whole genes or in the generation of so-called red-green hybrid genes (see Figure 2). More rarely, the photopigment genes, [23][24][25] or their promoter regions, 26 may contain point mutations.…”

Section: The Genetic Basis Of Congenital Colour Vision Deficiencymentioning

confidence: 99%