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
| العنوان: | 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 |
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| المؤلفون: | Nikolai O. Artemyev, Gaël Manes, Philippe Brabet, Audrey Sénéchal, Anurima Majumder, Christian P. Hamel, Pallavi Cheguru, Béatrice Bocquet |
| المصدر: | PLoS ONE, Vol 9, Iss 4, p e95768 (2014) PLoS ONE |
| بيانات النشر: | Public Library of Science (PLoS), 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | 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 |
| الوصف: | 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. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::02a682fa895aa3648d9a25b9de11b5d5 http://europepmc.org/articles/PMC3997432?pdf=render |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....02a682fa895aa3648d9a25b9de11b5d5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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