The phosphatidylinositol 4-kinase PI4KIIIα is required for the recruitment of GBF1 to Golgi membranes
The phosphatidylinositol 4-kinase PI4KIIIα is required for the recruitment of GBF1 to Golgi membranes
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DOI：
10.1242/jcs.055798
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发表时间：
2010-07-01
影响因子：
4
通讯作者：
Lefrancois, Stephane
中科院分区：
文献类型：
--
作者：
Dumaresq-Doiron, Karine;Savard, Marie-France;Lefrancois, Stephane
高尔基体的分选需要细胞质外壳蛋白的招募来将货物包装到运输囊泡中。转运囊泡形成的一个重要的早期步骤是鸟嘌呤核苷酸交换因子GBF1激活Arf1。为了激活Arf1， GBF1必须被募集到高尔基膜上并结合，这一过程需要Rab1b。然而，Rab1如何参与GBF1募集的机制细节尚不清楚。在本研究中，我们证明GBF1的募集也需要磷脂酰肌醇4-磷酸[PtdIns(4) P]。PtdIns(4) P合成抑制剂或PI4KIII α（一种定位于内质网和高尔基体的磷脂酰肌醇4-激酶）的耗竭可阻止GBF1向高尔基膜募集。有趣的是，通过PtdIns(4) P传感探针GFP-PH检测到，转染显性活性Rab1增加了高尔基体上PtdIns(4) P的数量。我们提出Rab1通过激活PI4KIII α来促进GBF1募集的特异性和时点。然后产生的PtdIns(4) P允许GBF1与高尔基膜结合并激活Arf1。
Sorting from the Golgi apparatus requires the recruitment of cytosolic coat proteins to package cargo into trafficking vesicles. An important early step in the formation of trafficking vesicles is the activation of Arf1 by the guanine nucleotide exchange factor GBF1. To activate Arf1, GBF1 must be recruited to and bound to Golgi membranes, a process that requires Rab1b. However, the mechanistic details of how Rab1 is implicated in GBF1 recruitment are not known. In this study, we demonstrate that the recruitment of GBF1 also requires phosphatidylinositol 4-phosphate [PtdIns(4) P]. Inhibitors of PtdIns(4) P synthesis or depletion of PI4KIII alpha, a phosphatidylinositol 4-kinase localized to the endoplasmic reticulum and Golgi, prevents the recruitment of GBF1 to Golgi membranes. Interestingly, transfection of dominant-active Rab1 increased the amount of PtdIns(4) P at the Golgi, as detected by GFP-PH, a PtdIns(4) P-sensing probe. We propose that Rab1 contributes to the specificity and timing of GBF1 recruitment by activating PI4KIII alpha. The PtdIns(4) P produced then allows GBF1 to bind to Golgi membranes and activate Arf1.