Garcia-Murillas Isaac, Pettitt Trevor, Macdonald Elaine, Okkenhaug Hanneke, Georgiev Plamen, Trivedi Deepti, Hassan Bassam, Wakelam Michael, Raghu Padinjat
Inositide Laboratory, Babraham Institute, Babraham Research Campus, Cambridge CB2 4AT, United Kingdom.
Neuron. 2006 Feb 16;49(4):533-46. doi: 10.1016/j.neuron.2006.02.001.
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.
果蝇光转导过程中的一个关键步骤是磷脂酶Cβ（PLCβ）水解磷脂酰肌醇4,5-二磷酸（PI(4,5)P2），生成一种第二信使，该信使可打开光激活通道TRP和TRPL。尽管这种信使的身份仍不清楚，但最近的证据表明，由rdgA编码的二酰基甘油激酶（DGK）是调节其水平的关键酶，介导放大作用和反应终止。在本研究中，我们证明了lazaro（laza）编码一种在光转导过程中发挥作用的脂质磷酸磷酸水解酶（LPP）。我们证明了laza和rdgA的协同活性调节光转导过程中的反应终止。视网膜磷脂分析显示磷脂酸（PA）水平降低，同时磷脂酰肌醇（PI）水平也相应降低。我们的结果共同证明了PI消耗对rdgA表型的影响，并提供了证据表明PI及其代谢产物的消耗可能是体内TRP通道激活的关键信号。
