National Key Laboratory of Plant Molecular Genetics, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese academy of Sciences, 200032 Shanghai, People's Republic of China.
Mol Plant. 2013 Sep;6(5):1692-702. doi: 10.1093/mp/sst076. Epub 2013 May 17.
Phospholipase D (PLD) exerts broad biological functions in eukaryotes through regulating downstream effectors by its product, phosphatidic acid (PA). Protein kinases and phosphatases, such as mammalian target of rapamycin (mTOR), Protein Phosphatase 1 (PP1) and Protein Phosphatase 2C (PP2C), are PA-binding proteins that execute crucial regulatory functions in both animals and plants. PA participates in many signaling pathways by modulating the enzymatic activity and/or subcellular localization of bound proteins. In this study, we demonstrated that PLD-derived PA interacts with the scaffolding A1 subunit of Protein Phosphatase 2A (PP2A) and regulates PP2A-mediated PIN1 dephosphorylation in Arabidopsis. Genetic and pharmacological studies showed that both PA and PP2A participate in the regulation of auxin distribution. In addition, both the phosphorylation status and polar localization of PIN1 protein were affected by PLD inhibitors. Exogenous PA triggered the membrane accumulation of PP2AA1 and enhanced the PP2A activity at membrane, while PLD inhibition resulted in the reduced endosomal localization and perinuclear aggregation of PP2AA1. These results demonstrate the important role of PLD-derived PA in normal PP2A-mediated PIN dephosphorylation and reveal a novel mechanism, in which PA recruits PP2AA1 to the membrane system and regulates PP2A function on membrane-targeted proteins. As PA and PP2A are conserved among eukaryotes, other organisms might use similar mechanisms to mediate multiple biological processes.
磷脂酶 D (PLD) 通过其产物磷脂酸 (PA) 调节下游效应物,在真核生物中发挥广泛的生物学功能。蛋白激酶和磷酸酶,如哺乳动物雷帕霉素靶蛋白 (mTOR)、蛋白磷酸酶 1 (PP1) 和蛋白磷酸酶 2C (PP2C),是 PA 结合蛋白,在动物和植物中执行关键的调节功能。PA 通过调节结合蛋白的酶活性和/或亚细胞定位参与许多信号通路。在本研究中,我们证明了 PLD 衍生的 PA 与蛋白磷酸酶 2A (PP2A) 的支架 A1 亚基相互作用,并调节拟南芥中 PP2A 介导的 PIN1 去磷酸化。遗传和药理学研究表明,PA 和 PP2A 都参与了生长素分布的调节。此外,PIN1 蛋白的磷酸化状态和极性定位都受到 PLD 抑制剂的影响。外源性 PA 触发 PP2AA1 的膜积累,并增强膜上的 PP2A 活性,而 PLD 抑制导致 PP2AA1 的内体定位减少和核周聚集。这些结果表明 PLD 衍生的 PA 在正常的 PP2A 介导的 PIN 去磷酸化中起着重要作用,并揭示了一种新的机制,即 PA 将 PP2AA1 募集到膜系统,并调节膜靶向蛋白上的 PP2A 功能。由于 PA 和 PP2A 在真核生物中是保守的,其他生物体可能使用类似的机制来介导多种生物学过程。