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.
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 phototra...
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0095768&type=printable |
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| author | Gaël Manes Pallavi Cheguru Anurima Majumder Béatrice Bocquet Audrey Sénéchal Nikolai O Artemyev Christian P Hamel Philippe Brabet |
| author_facet | Gaël Manes Pallavi Cheguru Anurima Majumder Béatrice Bocquet Audrey Sénéchal Nikolai O Artemyev Christian P Hamel Philippe Brabet |
| author_sort | Gaël Manes |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-7f003c8183e14ddb951cea4178a6b4b4 |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-7f003c8183e14ddb951cea4178a6b4b42025-08-20T03:00:30ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0194e9576810.1371/journal.pone.0095768A 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.Gaël ManesPallavi CheguruAnurima MajumderBéatrice BocquetAudrey SénéchalNikolai O ArtemyevChristian P HamelPhilippe BrabetAutosomal 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0095768&type=printable |
| spellingShingle | Gaël Manes Pallavi Cheguru Anurima Majumder Béatrice Bocquet Audrey Sénéchal Nikolai O Artemyev Christian P Hamel Philippe Brabet 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. PLoS ONE |
| title | 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. |
| title_full | 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. |
| title_fullStr | 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. |
| title_full_unstemmed | 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. |
| title_short | 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. |
| title_sort | 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 |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0095768&type=printable |
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