Raghu Padinjat, Coessens Elise, Manifava Maria, Georgiev Plamen, Pettitt Trevor, Wood Eleanor, Garcia-Murillas Isaac, Okkenhaug Hanneke, Trivedi Deepti, Zhang Qifeng, Razzaq Azam, Zaid Ola, Wakelam Michael, O'Kane Cahir J, Ktistakis Nicholas
Inositide Laboratory, Babraham Institute, Babraham Research Campus, Cambridge, England, UK.
J Cell Biol. 2009 Apr 6;185(1):129-45. doi: 10.1083/jcb.200807027.
Phosphatidic acid (PA) is postulated to have both structural and signaling functions during membrane dynamics in animal cells. In this study, we show that before a critical time period during rhabdomere biogenesis in Drosophila melanogaster photoreceptors, elevated levels of PA disrupt membrane transport to the apical domain. Lipidomic analysis shows that this effect is associated with an increase in the abundance of a single, relatively minor molecular species of PA. These transport defects are dependent on the activation state of Arf1. Transport defects via PA generated by phospholipase D require the activity of type I phosphatidylinositol (PI) 4 phosphate 5 kinase, are phenocopied by knockdown of PI 4 kinase, and are associated with normal endoplasmic reticulum to Golgi transport. We propose that PA levels are critical for apical membrane transport events required for rhabdomere biogenesis.
磷脂酸(PA)被认为在动物细胞膜动力学过程中具有结构和信号传导功能。在本研究中,我们发现,在黑腹果蝇光感受器小网膜发生的关键时期之前,PA水平升高会破坏向顶端区域的膜转运。脂质组学分析表明,这种效应与PA的一种相对较少的单一分子种类丰度增加有关。这些转运缺陷取决于Arf1的激活状态。由磷脂酶D产生的PA导致的转运缺陷需要I型磷脂酰肌醇(PI)4磷酸5激酶的活性,通过敲低PI 4激酶可模拟该现象,并且与内质网到高尔基体的正常转运相关。我们提出,PA水平对于小网膜发生所需的顶端膜转运事件至关重要。