Phosphoinositide 3-kinase signaling in retinal rod photoreceptors.
Invest Ophthalmol Vis Sci
; 52(9): 6355-62, 2011 Aug 11.
Article
em En
| MEDLINE
| ID: mdl-21730346
ABSTRACT
PURPOSE:
Phosphoinositide 3-kinase (PI3K) consists of a p110 catalytic protein and a p85α regulatory protein, required for the stabilization and localization of p110-PI3K activity. The biological significance of PI3K was investigated in vertebrate rod photoreceptors by deleting its regulatory p85α protein and examining its role in photoreceptor structure, function, and protein trafficking.METHODS:
Mice that expressed Cre recombinase in rods were bred to mice with a floxed p85α (pik3r1) regulatory subunit of PI3K to generate a conditional deletion of pik3r1 in rods. Functional and structural changes were determined by ERG and morphometric analysis, respectively. PI3K activity was measured in retinal homogenates immunoprecipitated with an anti-PY antibody. Akt activation was determined by Western blot analysis with a pAkt antibody.RESULTS:
Light-induced stress increased PI3K activity in retinal immunoprecipitates and phosphorylation of Akt. There was no effect of pik3r1 deletion on retinal structure. However, twin flash electroretinography revealed a slight delay in recovery kinetics in pik3r1 knockout (KO) mice compared with wild-type controls. The movement of arrestin in the pik3r1 KO mice was slower than that in the wild-type mouse retinas at 5 minutes of exposure to light. At 10 minutes of exposure, the ROS localization of arrestin was almost identical between the wild-type and pik3r1 KO mice.CONCLUSIONS:
The results provide the first direct evidence that rods use PI3K-generated phosphoinositides for photoreceptor function. The lack of phenotype in pik3r1 KO rod photoreceptors suggests a redundant role in controlling PIP(3) synthesis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Células Fotorreceptoras Retinianas Bastonetes
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Fosfatidilinositol 3-Quinase
Limite:
Animals
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article