lazaro encodes a lipid phosphate phosphohydrolase that regulates phosphatidylinositol turnover during Drosophila phototransduction.
An essential step in Drosophila phototransduction is the hydrolysis of phosphatidylinositol 4,5 bisphosphate PI(4,5)P2 by phospholipase Cbeta (PLCbeta) to generate a second messenger that opens the light-activated channels TRP and TRPL. Although the identity of this messenger remains unknown, recent evidence has implicated diacylglycerol kinase (DGK), encoded by rdgA, as a key enzyme that regulates its levels, mediating both amplification and response termination. In this study, we demonstrate that lazaro (laza) encodes a lipid phosphate phosphohydrolase (LPP) that functions during phototransduction. We demonstrate that the synergistic activity of laza and rdgA regulates response termination during phototransduction. Analysis of retinal phospholipids revealed a reduction in phosphatidic acid (PA) levels and an associated reduction in phosphatidylinositol (PI) levels. Together our results demonstrate the contribution of PI depletion to the rdgA phenotype and provide evidence that depletion of PI and its metabolites might be a key signal for TRP channel activation in vivo.
Inositide Laboratory, Babraham Institute, Babraham Research Campus, Cambridge CB2 4AT, United Kingdom.
Isaac
I
Garcia-Murillas
Trevor
T
Pettitt
Elaine
E
Macdonald
Hanneke
H
Okkenhaug
Plamen
P
Georgiev
Deepti
D
Trivedi
Bassam
B
Hassan
Michael
M
Wakelam
Padinjat
P
Raghu
D000367:Age Factors; D000818:Animals; D030801:Animals, Genetically Modified; D015152:Blotting, Northern / Q000379:methods; D019852:Diacylglycerol Kinase / Q000235:genetics / Q000378:metabolism; D004330:Drosophila / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004596:Electroretinography / Q000379:methods; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D050356:Lipid Metabolism / Q000502:physiology*; D008854:Microscopy, Electron / Q000379:methods; D008967:Molecular Biology / Q000379:methods; D016296:Mutagenesis / Q000502:physiology; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism*; D017956:Photoreceptor Cells, Invertebrate / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D012160:Retina / Q000378:metabolism; D012162:Retinal Degeneration / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D016415:Sequence Alignment; D014785:Vision, Ocular / Q000187:drug effects / Q000502:physiology*
D029721:Drosophila Proteins; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D012333:RNA, Messenger; D019852:Diacylglycerol Kinase; C509828:laza protein, Drosophila; D010744:Phosphoric Monoester Hydrolases