title: Phosphatidylinositol-3-phosphate is light-regulated and essential for survival in retinal rods.
abstract: Phosphoinositides play important roles in numerous intracellular membrane pathways. Little is known about the regulation or function of these lipids in rod photoreceptor cells, which have highly active membrane dynamics. Using new assays with femtomole sensitivity, we determined that whereas levels of phosphatidylinositol-3,4-bisphosphate and phosphatidylinositol-3,4,5-trisphosphate were below detection limits, phosphatidylinositol-3-phosphate (PI(3)P) levels in rod inner/outer segments increased more than 30-fold after light exposure. This increase was blocked in a rod-specific knockout of the PI-3 kinase Vps34, resulting in failure of endosomal and autophagy-related membranes to fuse with lysosomes, and accumulation of abnormal membrane structures. At early ages, rods displayed normal morphology, rhodopsin trafficking, and light responses, but underwent progressive neurodegeneration with eventual loss of both rods and cones by twelve weeks. The degeneration is considerably faster than in rod knockouts of autophagy genes, indicating defects in endosome recycling or other PI(3)P-dependent membrane trafficking pathways are also essential for rod survival.
authors.affiliation: Verna and Marrs McLean Department of Biochemistry and Molecular Biology , Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: He
authors.affiliation: Verna and Marrs McLean Department of Biochemistry and Molecular Biology , Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Melina A
authors.initials: MA
authors.lastname: Agosto
authors.affiliation: Verna and Marrs McLean Department of Biochemistry and Molecular Biology , Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Ivan A
authors.initials: IA
authors.lastname: Anastassov
authors.affiliation: Department of Ophthalmology, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA.|School of Optometry, The Hong Kong Polytechnic University, Hong Kong SAR, China.
authors.forename: Dennis Y
authors.initials: DY
authors.lastname: Tse
authors.affiliation: Department of Ophthalmology, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA.
authors.forename: Samuel M
authors.initials: SM
authors.lastname: Wu
authors.affiliation: Verna and Marrs McLean Department of Biochemistry and Molecular Biology , Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.|Department of Ophthalmology, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA.
authors.forename: Theodore G
authors.initials: TG
authors.lastname: Wensel
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics; D000071183:Autophagy-Related Proteins / Q000172:deficiency / Q000235:genetics; D002470:Cell Survival; D058546:Class III Phosphatidylinositol 3-Kinases / Q000172:deficiency / Q000235:genetics*; D011992:Endosomes / Q000378:metabolism; D005786:Gene Expression Regulation; D008027:Light; D055537:Light Signal Transduction; D008247:Lysosomes / Q000378:metabolism; D008561:Membrane Fusion; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism* / Q000473:pathology; D012162:Retinal Degeneration / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism* / Q000473:pathology; D012243:Rhodopsin / Q000235:genetics* / Q000378:metabolism
chemical_list: D000071183:Autophagy-Related Proteins; D018129:Phosphatidylinositol Phosphates; C055525:phosphatidylinositol 3-phosphate; D012243:Rhodopsin; D058546:Class III Phosphatidylinositol 3-Kinases