title: Regulation of phototransduction responsiveness and retinal degeneration by a phospholipase D-generated signaling lipid.
abstract: Drosophila melanogaster phototransduction proceeds via a phospholipase C (PLC)-triggered cascade of phosphatidylinositol (PI) lipid modifications, many steps of which remain undefined. We describe the involvement of the lipid phosphatidic acid and the enzyme that generates it, phospholipase D (Pld), in this process. Pld(null) flies exhibit decreased light sensitivity as well as a heightened susceptibility to retinal degeneration. Pld overexpression rescues flies lacking PLC from light-induced, metarhodopsin-mediated degeneration and restores visual signaling in flies lacking the PI transfer protein, which is a key player in the replenishment of the PI 4,5-bisphosphate (PIP2) substrate used by PLC to transduce light stimuli into neurological signals. Altogether, these findings suggest that Pld facilitates phototransduction by maintaining adequate levels of PIP2 and by protecting the visual system from metarhodopsin-induced, low light degeneration.
authors.affiliation: Program in Molecular and Cellular Biology, Center for Developmental Genetics, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Mary M
authors.initials: MM
authors.lastname: LaLonde
authors.forename: Hilde
authors.initials: H
authors.lastname: Janssens
authors.forename: Erica
authors.initials: E
authors.lastname: Rosenbaum
authors.forename: Seok-Yong
authors.initials: SY
authors.lastname: Choi
authors.forename: J Peter
authors.initials: JP
authors.lastname: Gergen
authors.forename: Nansi J
authors.initials: NJ
authors.lastname: Colley
authors.forename: William S
authors.initials: WS
authors.lastname: Stark
authors.forename: Michael A
authors.initials: MA
authors.lastname: Frohman
mesh_terms: D000818:Animals; D004331:Drosophila melanogaster / Q000201:enzymology* / Q000648:ultrastructure; D008027:Light / Q000009:adverse effects; D008565:Membrane Proteins / Q000378:metabolism; D009154:Mutation / Q000502:physiology; D010712:Phosphatidic Acids / Q000378:metabolism; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D010739:Phospholipase D / Q000235:genetics / Q000378:metabolism*; D049294:Phospholipid Transfer Proteins / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D017956:Photoreceptor Cells, Invertebrate / Q000201:enzymology* / Q000648:ultrastructure; D012160:Retina / Q000201:enzymology* / Q000648:ultrastructure; D012162:Retinal Degeneration / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D012243:Rhodopsin / Q000378:metabolism / Q000528:radiation effects; D010738:Type C Phospholipases / Q000378:metabolism; D014785:Vision, Ocular / Q000502:physiology*
chemical_list: D008565:Membrane Proteins; D010712:Phosphatidic Acids; D019269:Phosphatidylinositol 4,5-Diphosphate; D049294:Phospholipid Transfer Proteins; D010743:Phospholipids; C013110:metarhodopsins; D012243:Rhodopsin; D010738:Type C Phospholipases; D010739:Phospholipase D