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A truncated form of rod photoreceptor PDE6 β-subunit causes autosomal dominant congenital stationary night blindness by interfering with the inhibitory activity of the γ-subunit
- Source :
- PLoS ONE, Vol 9, Iss 4, p e95768 (2014), PLoS ONE
- Publication Year :
- 2014
- Publisher :
- Public Library of Science (PLoS), 2014.
-
Abstract
- Autosomal dominant congenital stationary night blindness (adCSNB) is caused by mutations in three genes of the rod phototransduction cascade, rhodopsin (RHO), transducin α-subunit (GNAT1), and cGMP phosphodiesterase type 6 β-subunit (PDE6B). In most cases, the constitutive activation of the phototransduction cascade is a prerequisite to cause adCSNB. The unique adCSNB-associated PDE6B mutation found in the Rambusch pedigree, the substitution p.His258Asn, leads to rod photoreceptors desensitization. Here, we report a three-generation French family with adCSNB harboring a novel PDE6B mutation, the duplication, c.928-9_940dup resulting in a tyrosine to cysteine substitution at codon 314, a frameshift, and a premature termination (p.Tyr314Cysfs*50). To understand the mechanism of the PDE6β1-314fs*50 mutant, we examined the properties of its PDE6-specific portion, PDE6β1-313. We found that PDE6β1-313 maintains the ability to bind noncatalytic cGMP and the inhibitory γ-subunit (Pγ), and interferes with the inhibition of normal PDE6αβ catalytic subunits by Pγ. Moreover, both truncated forms of the PDE6β protein, PDE6β1-313 and PDE6β1-314fs*50 expressed in rods of transgenic X. laevis are targeted to the phototransduction compartment. We hypothesize that in affected family members the p.Tyr314Cysfs*50 change results in the production of the truncated protein, which binds Pγ and causes constitutive activation of the phototransduction thus leading to the absence of rod adaptation.
- Subjects :
- Visual System
Agricultural Biotechnology
Xenopus
lcsh:Medicine
Biochemistry
Animals, Genetically Modified
Xenopus laevis
Night Blindness
Catalytic Domain
Medicine and Health Sciences
Myopia
lcsh:Science
GNAT1
Multidisciplinary
Genetically Modified Organisms
Agriculture
Eye Diseases, Hereditary
Genetic Diseases, X-Linked
Animal Models
Heterotrimeric GTP-Binding Proteins
Sensory Systems
Rhodopsin
Vertebrates
Frogs
Retinal Disorders
Transducin
Transgenic Animals
Research Article
Visual phototransduction
Light Signal Transduction
Nonsense mutation
Biology
Research and Analysis Methods
Frameshift mutation
Amphibians
Model Organisms
PDE6B
Retinitis pigmentosa
Genetics
medicine
Animals
Humans
Inherited Eye Disorders
Cyclic Nucleotide Phosphodiesterases, Type 6
lcsh:R
Organisms
Biology and Life Sciences
Proteins
medicine.disease
Molecular biology
Ophthalmology
Mutation
biology.protein
lcsh:Q
sense organs
Neuroscience
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 9
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....02a682fa895aa3648d9a25b9de11b5d5