title: Phosphoinositide 3-kinase signaling in retinal rod photoreceptors.
abstract: OBJECTIVE
  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.
authors: Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA.
authors: Ivana
authors: I
authors: Ivanovic
authors: Dustin T
authors: DT
authors: Allen
authors: Radhika
authors: R
authors: Dighe
authors: Yun Z
authors: YZ
authors: Le
authors: Robert E
authors: RE
authors: Anderson
authors: Raju V S
authors: RV
authors: Rajala
mesh_terms: D000818:Animals; D019393:Arrestin / Q000378:metabolism; D015153:Blotting, Western; D058543:Class Ia Phosphatidylinositol 3-Kinase / Q000235:genetics; D004596:Electroretinography; D017353:Gene Deletion; D019426:Integrases / Q000235:genetics; D008027:Light / Q000009:adverse effects; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D058539:Phosphatidylinositol 3-Kinase / Q000502:physiology*; D010766:Phosphorylation; D010775:Photic Stimulation; D021381:Protein Transport; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011833:Radiation Injuries, Experimental / Q000201:enzymology; D051381:Rats; D012162:Retinal Degeneration / Q000201:enzymology; D017948:Retinal Rod Photoreceptor Cells / Q000201:enzymology* / Q000528:radiation effects; D012243:Rhodopsin / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D015293:Transducin / Q000378:metabolism
chemical_list: D019393:Arrestin; D012243:Rhodopsin; D058543:Class Ia Phosphatidylinositol 3-Kinase; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; C045073:Cre recombinase; D019426:Integrases; D015293:Transducin