Leung Hung-Tat, Tseng-Crank Julie, Kim Eunju, Mahapatra Cecon, Shino Shikoh, Zhou Ying, An Lingling, Doerge Rebecca W, Pak William L
Department of Biological Sciences, Purdue University, West Lafayette, IN 47907-2054, USA.
Neuron. 2008 Jun 26;58(6):884-96. doi: 10.1016/j.neuron.2008.05.001.
In Drosophila, a phospholipase C-mediated signaling cascade links photoexcitation of rhodopsin to the opening of the TRP/TRPL channels. A lipid product of the cascade, diacylglycerol (DAG) and its metabolite(s), polyunsaturated fatty acids (PUFAs), have both been proposed as potential excitatory messengers. A crucial enzyme in the understanding of this process is likely to be DAG lipase (DAGL). However, DAGLs that might fulfill this role have not been previously identified in any organism. In this work, the Drosophila DAGL gene, inaE, has been identified from mutants that are defective in photoreceptor responses to light. The inaE-encoded protein isoforms show high sequence similarity to known mammalian DAG lipases, exhibit DAG lipase activity in vitro, and are highly expressed in photoreceptors. Analyses of norpA inaE double mutants and severe inaE mutants show that normal DAGL activity is required for the generation of physiologically meaningful photoreceptor responses.
在果蝇中，磷脂酶C介导的信号级联反应将视紫红质的光激发与TRP/TRPL通道的开放联系起来。该级联反应的一种脂质产物二酰基甘油（DAG）及其代谢物多不饱和脂肪酸（PUFA）都被认为是潜在的兴奋性信使。理解这一过程的关键酶可能是DAG脂肪酶（DAGL）。然而，此前在任何生物体中都未鉴定出可能发挥这一作用的DAGL。在这项研究中，从对光的光感受器反应有缺陷的突变体中鉴定出了果蝇DAGL基因inaE。inaE编码的蛋白质异构体与已知的哺乳动物DAG脂肪酶具有高度的序列相似性，在体外表现出DAG脂肪酶活性，并且在光感受器中高度表达。对norpA inaE双突变体和严重inaE突变体的分析表明，正常的DAGL活性是产生具有生理意义的光感受器反应所必需的。
