lazaro Encodes a Lipid Phosphate Phosphohydrolase that Regulates Phosphatidylinositol Turnover during Drosophila Phototransduction

• DOI: 10.1016/j.neuron.2006.02.001
• Publication Date: 2006-02-16T12:21:15Z
• Authors: Isaac Garcia-Muri...; Trevor Pettitt; Elaine Macdonald; Hanneke Okkenhaug; Plamen Georgiev; Deepti Trivedi; Bassam Hassan; Michael Wakelam; Padinjat Raghu
• Keywords: Phosphatidylinositol 4,5-Diphosphate; 0301 basic medicine; Diacylglycerol Kinase; Neuroscience(all); Gene Expression; Phosphatidylinositols; MOLNEURO; Animals, Genetically Modified; 03 medical and health sciences; Electroretinography; Animals; Drosophila Proteins; Humans; RNA, Messenger; Molecular Biology; 0303 health sciences; Age Factors; Blotting, Northern; Lipid Metabolism; Immunohistochemistry; Phosphoric Monoester Hydrolases; Microscopy, Electron; SIGNALING; Mutagenesis; Drosophila; Photoreceptor Cells, Invertebrate

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.