Defective Intracellular Transport is the Molecular Basis of Rhodopsin- Dependent Dominant Retinal Degeneration

Retinitis pigmentosa (RP) is a group of hereditary human diseases that cause retinal degeneration and lead to eventual blindness. More than 25% of all RP cases in humans appear to be caused by dominant mutations in the gene encoding the visual pigment rhodopsin. The mechanism by which the mutant rho...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1995-03, Vol.92 (7), p.3070-3074
Main Authors: Colley, Nansi J., Cassill, J. Aaron, Baker, Elizabeth K., Zuker, Charles S.
Format: Article
Language:English
Subjects:
Alleles
Amino Acid Sequence
Animals
Biological Transport
Cloning, Molecular
Drosophila
Drosophila - genetics
Electroretinography
Endoplasmic Reticulum - metabolism
Endoplasmic Reticulum - ultrastructure
Ethyl Methanesulfonate
Eyes & eyesight
Genes, Dominant
Genetic mutation
Genetic screening
Genetics
Human genetics
Medical genetics
Molecular biology
Molecular Sequence Data
Molecules
Mutagenesis
Mutation
Phenotypes
Photoreceptor Cells - metabolism
Photoreceptor Cells - ultrastructure
Photoreceptor Cells, Invertebrate
Photoreceptors
Point Mutation
Protein Folding
Protein Structure, Secondary
Proteins
Recombinant Proteins - chemistry
Recombinant Proteins - metabolism
Retinal degeneration
Retinal Degeneration - genetics
Retinal Degeneration - physiopathology
Retinitis Pigmentosa - genetics
Rhodopsin - chemistry
Rhodopsin - genetics
Rhodopsin - metabolism
Rod Opsins - genetics
Rod Opsins - metabolism
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Description
Summary:Retinitis pigmentosa (RP) is a group of hereditary human diseases that cause retinal degeneration and lead to eventual blindness. More than 25% of all RP cases in humans appear to be caused by dominant mutations in the gene encoding the visual pigment rhodopsin. The mechanism by which the mutant rhodopsin proteins cause dominant retinal degeneration is still unclear. Interestingly, the great majority of these mutants appear to produce misfolded rhodopsin. We now report the isolation and characterization of 13 rhodopsin mutations that act dominantly to cause retinal degeneration in Drosophila; four of these correspond to identical substitutions in human autosomal dominant RP patients. We demonstrate that retinal degeneration results from interference in the maturation of wild-type rhodopsin by the mutant proteins.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.92.7.3070