Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Neurosci
2004 Mar 10;2410:2516-26. doi: 10.1523/JNEUROSCI.5426-03.2004.
Show Gene links
Show Anatomy links
Novel dominant rhodopsin mutation triggers two mechanisms of retinal degeneration and photoreceptor desensitization.
Iakhine R
,
Chorna-Ornan I
,
Zars T
,
Elia N
,
Cheng Y
,
Selinger Z
,
Minke B
,
Hyde DR
.
???displayArticle.abstract???
A variety of rod opsin mutations result in autosomal dominant retinitis pigmentosa and congenital night blindness in humans. One subset of these mutations encodes constitutively active forms of the rod opsin protein. Some of these dominant rod opsin mutant proteins, which desensitize transgenic Xenopus rods, provide an animal model for congenital night blindness. In a genetic screen to identify retinal degeneration mutants in Drosophila, we identified a dominant mutation in the ninaE gene (NinaE(pp100)) that encodes the rhodopsin that is expressed in photoreceptors R1-R6. Deep pseudopupil analysis and histology showed that the degeneration was attributable to a light-independent apoptosis. Whole-cell recordings revealed that the NinaE(pp100) mutant photoreceptor cells were strongly desensitized, which partially masked their constitutive activity. This desensitization primarily resulted from both the persistent binding of arrestin (ARR2) to the NINAE(pp100) mutant opsin and the constitutive activity of the phototransduction cascade. Whereas mutations in several Drosophila genes other than ninaE were shown to induce photoreceptor cell apoptosis by stabilizing a rhodopsin-arrestin complex, NinaE(pp100) represented the first rhodopsin mutation that stabilized this protein complex. Additionally, the NinaE(pp100) mutation led to elevated levels of G(q)alpha in the cytosol, which mediated a novel retinal degeneration pathway. Eliminating both G(q)alpha and arrestin completely rescued the NinaE(pp100)-dependent photoreceptor cell death, which indicated that the degeneration is entirely dependent on both G(q)alpha and arrestin. Such a combination of multiple pathological pathways resulting from a single mutation may underlie several dominant retinal diseases in humans.
Alloway,
A role for the light-dependent phosphorylation of visual arrestin.
1999, Pubmed
Alloway,
A role for the light-dependent phosphorylation of visual arrestin.
1999,
Pubmed
Alloway,
The formation of stable rhodopsin-arrestin complexes induces apoptosis and photoreceptor cell degeneration.
2000,
Pubmed
Blumenfeld,
Light-activated guanosinetriphosphatase in Musca eye membranes resembles the prolonged depolarizing afterpotential in photoreceptor cells.
1985,
Pubmed
Byk,
Regulatory arrestin cycle secures the fidelity and maintenance of the fly photoreceptor cell.
1993,
Pubmed
Colley,
Defective intracellular transport is the molecular basis of rhodopsin-dependent dominant retinal degeneration.
1995,
Pubmed
Cook,
Phospholipase C and termination of G-protein-mediated signalling in vivo.
2000,
Pubmed
Dolph,
Arrestin function in inactivation of G protein-coupled receptor rhodopsin in vivo.
1993,
Pubmed
Dryja,
Molecular genetics of Oguchi disease, fundus albipunctatus, and other forms of stationary night blindness: LVII Edward Jackson Memorial Lecture.
2000,
Pubmed
Dryja,
Heterozygous missense mutation in the rhodopsin gene as a cause of congenital stationary night blindness.
1993,
Pubmed
Hao,
Evidence for two apoptotic pathways in light-induced retinal degeneration.
2002,
Pubmed
Hardie,
The trp gene is essential for a light-activated Ca2+ channel in Drosophila photoreceptors.
1992,
Pubmed
Hardie,
Voltage-sensitive potassium channels in Drosophila photoreceptors.
1991,
Pubmed
Hardie,
Spontaneous activation of light-sensitive channels in Drosophila photoreceptors.
1994,
Pubmed
Hillman,
Transduction in invertebrate photoreceptors: role of pigment bistability.
1983,
Pubmed
Jin,
Opsin activation as a cause of congenital night blindness.
2003,
Pubmed
,
Xenbase
Johnson,
Electrophysiological study of Drosophila rhodopsin mutants.
1986,
Pubmed
Kaushal,
Structure and function in rhodopsin. 7. Point mutations associated with autosomal dominant retinitis pigmentosa.
1994,
Pubmed
Kiselev,
A molecular pathway for light-dependent photoreceptor apoptosis in Drosophila.
2000,
Pubmed
Kiselev,
Activation and regeneration of rhodopsin in the insect visual cycle.
1994,
Pubmed
Kosloff,
Regulation of light-dependent Gqalpha translocation and morphological changes in fly photoreceptors.
2003,
Pubmed
Kurada,
Retinal degeneration caused by dominant rhodopsin mutations in Drosophila.
1995,
Pubmed
Kurada,
Rhodopsin maturation antagonized by dominant rhodopsin mutants.
1998,
Pubmed
Lee,
dgq: a drosophila gene encoding a visual system-specific G alpha molecule.
1990,
Pubmed
Lee,
The Drosophila dgq gene encodes a G alpha protein that mediates phototransduction.
1994,
Pubmed
Leonard,
Degeneration of photoreceptors in rhodopsin mutants of Drosophila.
1992,
Pubmed
Li,
Constitutive activation of phototransduction by K296E opsin is not a cause of photoreceptor degeneration.
1995,
Pubmed
Milligan,
The phosphatidylinositol transfer protein domain of Drosophila retinal degeneration B protein is essential for photoreceptor cell survival and recovery from light stimulation.
1997,
Pubmed
Min,
Characterization of mutant rhodopsins responsible for autosomal dominant retinitis pigmentosa. Mutations on the cytoplasmic surface affect transducin activation.
1993,
Pubmed
O'Tousa,
The Drosophila ninaE gene encodes an opsin.
1985,
Pubmed
Paetkau,
Isolation and characterization of Drosophila retinal degeneration B suppressors.
1999,
Pubmed
Peretz,
The light response of Drosophila photoreceptors is accompanied by an increase in cellular calcium: effects of specific mutations.
1994,
Pubmed
Phelan,
A brief review of retinitis pigmentosa and the identified retinitis pigmentosa genes.
2000,
Pubmed
Raghu,
Constitutive activity of the light-sensitive channels TRP and TRPL in the Drosophila diacylglycerol kinase mutant, rdgA.
2000,
Pubmed
Rao,
Rhodopsin mutation G90D and a molecular mechanism for congenital night blindness.
1994,
Pubmed
Rattner,
Molecular genetics of human retinal disease.
1999,
Pubmed
Rim,
Constitutive activation of opsin: interaction of mutants with rhodopsin kinase and arrestin.
1995,
Pubmed
Robinson,
Constitutively active mutants of rhodopsin.
1992,
Pubmed
Rochdi,
Galphaq-coupled receptor internalization specifically induced by Galphaq signaling. Regulation by EBP50.
2003,
Pubmed
Roof,
Rhodopsin accumulation at abnormal sites in retinas of mice with a human P23H rhodopsin transgene.
1994,
Pubmed
Scott,
Gq alpha protein function in vivo: genetic dissection of its role in photoreceptor cell physiology.
1995,
Pubmed
Shetty,
Rab6 regulation of rhodopsin transport in Drosophila.
1998,
Pubmed
Sung,
A rhodopsin gene mutation responsible for autosomal dominant retinitis pigmentosa results in a protein that is defective in localization to the photoreceptor outer segment.
1994,
Pubmed
Vihtelic,
Isolation and characterization of the Drosophila retinal degeneration B (rdgB) gene.
1991,
Pubmed
Vihtelic,
Localization of Drosophila retinal degeneration B, a membrane-associated phosphatidylinositol transfer protein.
1993,
Pubmed
Wang,
Update on the molecular genetics of retinitis pigmentosa.
2001,
Pubmed
Yoon,
Novel mechanism of massive photoreceptor degeneration caused by mutations in the trp gene of Drosophila.
2000,
Pubmed
Zuker,
Isolation and structure of a rhodopsin gene from D. melanogaster.
1985,
Pubmed
