Regulation of phototransduction responsiveness and retinal degeneration by a phospholipase D-generated signaling lipid.
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.
LaLonde
Mary M
MM
Program in Molecular and Cellular Biology, Center for Developmental Genetics, Stony Brook University, Stony Brook, NY 11794, USA.
Janssens
Hilde
H
Rosenbaum
Erica
E
Choi
Seok-Yong
SY
Gergen
J Peter
JP
Colley
Nansi J
NJ
Stark
William S
WS
Frohman
Michael A
MA
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*
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