The phosphatidylinositol-transfer protein Nir2 binds phosphatidic acid and positively regulates phosphoinositide signalling
The phosphatidylinositol-transfer protein Nir2 binds phosphatidic acid and positively regulates phosphoinositide signalling
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DOI：
10.1038/embor.2013.113
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发表时间：
2013-10-01
期刊：
影响因子：
7.7
通讯作者：
Lev, Sima
中科院分区：
文献类型：
--
作者：
Kim, Sohui;Kedan, Amir;Lev, Sima
磷脂酸(PA)和磷脂酰肌醇是代谢相互转换的脂质第二信使，在许多生长因子(GF)刺激的信号通路中发挥核心作用。然而，人们对协调它们的生产和下游信号传递的机制知之甚少。在这里，我们展示了磷脂酰肌醇(PI)转移蛋白Nir2从高尔基复合体转移到质膜，以响应生长因子的刺激。这种易位是由PA的形成触发的，并由其在体外与PA结合的C末端区域介导。我们进一步表明，Nir2的缺乏显著降低了质膜上PI(4，5)P2的水平，并伴随着GF刺激的PI(3，4，5)P3的产生。最后，我们发现Nir2正向调节MAPK和PI3K/AKT通路。我们认为，Nir2通过其PA结合能力和PI传递活性，可以将PA与肌醇磷脂信号偶联，并可能协调它们的局部脂代谢和下游信号。
Phosphatidic acid (PA) and phosphoinositides are metabolically interconverted lipid second messengers that have central roles in many growth factor (GF)-stimulated signalling pathways. Yet, little is known about the mechanisms that coordinate their production and downstream signalling. Here we show that the phosphatidylinositol (PI)-transfer protein Nir2 translocates from the Golgi complex to the plasma membrane in response to GF stimulation. This translocation is triggered by PA formation and is mediated by its C-terminal region that binds PA in vitro. We further show that depletion of Nir2 substantially reduces the PI(4,5)P2 levels at the plasma membrane and concomitantly GF-stimulated PI(3,4,5)P3 production. Finally, we show that Nir2 positively regulates the MAPK and PI3K/AKT pathways. We propose that Nir2 through its PA-binding capability and PI-transfer activity can couple PA to phosphoinositide signalling, and possibly coordinates their local lipid metabolism and downstream signalling.