Recruitment of arfaptins to the trans-Golgi network by PI(4)P and their involvement in cargo export
Recruitment of arfaptins to the trans-Golgi network by PI(4)P and their involvement in cargo export
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DOI：
10.1038/emboj.2013.116
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发表时间：
2013-06-12
期刊：
影响因子：
11.4
通讯作者：
Malhotra, Vivek
中科院分区：
文献类型：
--
作者：
Cruz-Garcia, David;Ortega-Bellido, Maria;Malhotra, Vivek
BAR（Bin/Amphiphysin/Rvs）结构域蛋白arfaptin 1和arfaptin 2定位于高尔基体网络（trans-Golgi network，TGN），并且凭借其感知和/或产生膜曲率的能力，在运输载体的生物发生中可能发挥重要作用。我们报道arfaptins在BAR结构域之前含有一个两亲性螺旋（AH），这对于它们与含磷脂酰肌醇4-磷酸（PI（4）P）的脂质体和哺乳动物细胞的TGN结合是必不可少的。arfaptin 1（而非arfaptin 2）与PI（4）P的结合受蛋白激酶D（PKD）介导的AH内Ser 100磷酸化的调节。我们还发现，只有arfaptin 1所需的PKD依赖性运输的嗜铬粒蛋白A的调节分泌途径。总之，这些发现揭示了PI（4）P和PKD在TGN招募arfaptins中的重要性，以及它们在导致分泌储存颗粒生物发生的事件中的需求。
The BAR (Bin/Amphiphysin/Rvs) domain proteins arfaptin1 and arfaptin2 are localized to the trans-Golgi network (TGN) and, by virtue of their ability to sense and/or generate membrane curvature, could play an important role in the biogenesis of transport carriers. We report that arfaptins contain an amphipathic helix (AH) preceding the BAR domain, which is essential for their binding to phosphatidylinositol 4-phosphate (PI(4)P)-containing liposomes and the TGN of mammalian cells. The binding of arfaptin1, but not arfaptin2, to PI(4)P is regulated by protein kinase D (PKD) mediated phosphorylation at Ser100 within the AH. We also found that only arfaptin1 is required for the PKD-dependent trafficking of chromogranin A by the regulated secretory pathway. Altogether, these findings reveal the importance of PI(4)P and PKD in the recruitment of arfaptins at the TGN and their requirement in the events leading to the biogenesis of secretory storage granules.