Synthetic genetic array analysis of the PtdIns 4-kinase Pik1p identifies components in a golgi-specific Ypt31/rab-GTPase signaling pathway
Synthetic genetic array analysis of the PtdIns 4-kinase Pik1p identifies components in a golgi-specific Ypt31/rab-GTPase signaling pathway
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DOI：
10.1091/mbc.e04-08-0700
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发表时间：
2005-02-01
影响因子：
3.3
通讯作者：
Emr, SD
中科院分区：
文献类型：
--
作者：
Sciorra, VA;Audhya, A;Emr, SD
磷脂酰肌醇的磷酸化衍生物是真核细胞内吞和外吞运输的重要调节剂。在酿酒酵母中，磷脂酰肌醇4-激酶Pik 1 p产生一个独特的Ptdlns（4）P库，这是正常高尔基体结构和分泌功能所必需的。在这里，我们利用条件pik 1突变体的合成基因阵列分析，以确定在高尔基体的Pik 1 p/PtdIns（4）P信号通路的候选组件。我们的数据表明Pik 1 p与高尔基体相关蛋白的特定子集（包括Ypt 31 p rab-GTdR和TRAPPII蛋白复合物）的机械参与，通过分泌途径调节蛋白质运输。我们进一步证明TRAPPII特异性地在Ypt 31 p依赖性途径中起作用，并将Gyp 2 p鉴定为Ypt 31 p的第一个生物学相关的GT3活化蛋白。我们认为，Pik 1 p/PtdIns（4）P、TRAPPII和Gyp 2 p等多个阶段特异性信号参与了Ypt 31信号通路对高尔基体分泌功能的调控。
Phosphorylated derivatives of phosphatidylinositol are essential regulators of both endocytic and exocytic trafficking in eukaryotic cells. In Saccharomyces cerevisiae, the phosphatidylinositol 4-kinase, Pik1p generates a distinct pool of Ptdlns(4)P that is required for normal Golgi structure and secretory function. Here, we utilize a synthetic genetic array analysis of a conditional pik1 mutant to identify candidate components of the Pik1p/PtdIns(4)P signaling pathway at the Golgi. Our data suggest a mechanistic involvement for Pik1p with a specific subset of Golgi-associated proteins, including the Ypt31p rab-GTPase and the TRAPPII protein complex, to regulate protein trafficking through the secretory pathway. We further demonstrate that TRAPPII specifically functions in a Ypt31p-dependent pathway and identify Gyp2p as the first biologically relevant GTPase activating protein for Ypt31p. We propose that multiple stage-specific signals, which may include Pik1p/PtdIns(4)P, TRAPPII and Gyp2p, impinge upon Ypt31 signaling to regulate Golgi secretory function.