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Mendeley readers
Attention Score in Context
| Title |
Cone Phosphodiesterase-6γ’ Subunit Augments Cone PDE6 Holoenzyme Assembly and Stability in a Mouse Model Lacking Both Rod and Cone PDE6 Catalytic Subunits
|
|---|---|
| Published in |
Frontiers in Molecular Neuroscience, July 2018
|
| DOI | 10.3389/fnmol.2018.00233 |
| Pubmed ID | |
| Authors |
Wen-Tao Deng, Saravanan Kolandaivelu, Astra Dinculescu, Jie Li, Ping Zhu, Vince A. Chiodo, Visvanathan Ramamurthy, William W. Hauswirth |
| Abstract |
Rod and cone phosphodiesterase 6 (PDE6) are key effector enzymes of the vertebrate phototransduction pathway. Rod PDE6 consists of two catalytic subunits PDE6α and PDE6β and two identical inhibitory PDE6γ subunits, while cone PDE6 is composed of two identical PDE6α' catalytic subunits and two identical cone-specific PDE6γ' inhibitory subunits. Despite their prominent function in regulating cGMP levels and therefore rod and cone light response properties, it is not known how each subunit contributes to the functional differences between rods and cones. In this study, we generated an rd10/cpfl1 mouse model lacking rod PDE6β and cone PDE6α' subunits. Both rod and cone photoreceptor cells are degenerated with age and all PDE6 subunits degrade in rd10/cpfl1 mice. We expressed cone PDE6α' in both rods and cones of rd10/cpfl1 mice by adeno-associated virus (AAV)-mediated delivery driven by the ubiquitous, constitutive small chicken β-actin promoter. We show that expression of PDE6α' rescues rod function in rd10/cpfl1 mice, and the restoration of rod light sensitivity is attained through restoration of endogenous rod PDE6γ and formation of a functional PDE6α'γ complex. However, improved photopic cone responses were achieved only after supplementation of both cone PDE6α' and PDE6γ' subunits but not by PDE6α' treatment alone. We observed a two fold increase of PDE6α' levels in the eyes injected with both PDE6α' plus PDE6γ' relative to eyes receiving PDE6α' alone. Despite the presence of both PDE6γ' and PDE6γ, the majority of PDE6α' formed functional complexes with PDE6γ', suggesting that PDE6α' has a higher association affinity for PDE6γ' than for PDE6γ. These results suggest that the presence of PDE6γ' augments cone PDE6 assembly and enhances its stability. Our finding has important implication for gene therapy of PDE6α'-associated achromatopsia. |
X Demographics
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Switzerland | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 10 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 10 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 4 | 40% |
| Unspecified | 1 | 10% |
| Librarian | 1 | 10% |
| Other | 1 | 10% |
| Unknown | 3 | 30% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 3 | 30% |
| Agricultural and Biological Sciences | 2 | 20% |
| Unspecified | 1 | 10% |
| Medicine and Dentistry | 1 | 10% |
| Unknown | 3 | 30% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 14 July 2018.
All research outputs
#20,527,576
of 23,096,849 outputs
Outputs from Frontiers in Molecular Neuroscience
#2,507
of 2,930 outputs
Outputs of similar age
#286,161
of 326,642 outputs
Outputs of similar age from Frontiers in Molecular Neuroscience
#103
of 116 outputs
Altmetric has tracked 23,096,849 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,930 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.7. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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We're also able to compare this research output to 116 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.