Phosphatidylinositol 4,5-bisphosphate mediates the targeting of the exocyst to the plasma membrane for exocytosis in mammalian cells
Phosphatidylinositol 4,5-bisphosphate mediates the targeting of the exocyst to the plasma membrane for exocytosis in mammalian cells
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DOI：
10.1091/mbc.e07-05-0461
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发表时间：
2007-11-01
影响因子：
3.3
通讯作者：
Guo, Wei
中科院分区：
文献类型：
--
作者：
Liu, Jianglan;Zuo, Xiaofeng;Guo, Wei
外泌囊是一种进化上保守的八聚体蛋白复合物，它将高尔基体后分泌囊泡拴在质膜上进行胞吐作用。为了阐明囊泡束缚的机制，重要的是要了解外囊如何与质膜（PM）物理关联。在这项研究中，我们报告，哺乳动物外囊亚基Exo 70协会与PM通过其直接与磷脂酰肌醇4，5-二磷酸（PI（4，5）P-2）的相互作用。此外，我们已经鉴定了在Exo 70的C-末端的关键保守残基，其对于Exo 70与PI（4，5）P-2的相互作用至关重要。破坏Exo 70-PI（4，5）P-2相互作用消除了Exo 70的膜缔合。我们还发现，野生型Exo 70而非PI（4，5）P-2结合缺陷型Exo 70突变体能够将其他外囊组分募集至PM。使用ts 045水泡性口炎病毒糖蛋白运输试验，我们证明，Exo 70-PI（4，5）P-2相互作用是至关重要的对接和融合后高尔基体分泌囊泡，但不是他们的运输到PM。
The exocyst is an evolutionarily conserved octameric protein complex that tethers post-Golgi secretory vesicles at the plasma membrane for exocytosis. To elucidate the mechanism of vesicle tethering, it is important to understand how the exocyst physically associates with the plasma membrane (PM). In this study, we report that the mammalian exocyst subunit Exo70 associates with the PM through its direct interaction with phosphatidylinositol 4,5-bisphosphate (PI(4,5)P-2). Furthermore, we have identified key conserved residues at the C-terminus of Exo70 that are crucial for the interaction of Exo70 with PI(4,5)P-2. Disrupting Exo70-PI(4,5)P-2 interaction abolished the membrane association of Exo70. We have also found that wild-type Exo70 but not the PI(4,5)P-2-binding-deficient Exo70 mutant is capable of recruiting other exocyst components to the PM. Using the ts045 vesicular stomatitis virus glycoprotein trafficking assay, we demonstrate that Exo70-PI(4,5)P-2 interaction is critical for the docking and fusion of post-Golgi secretory vesicles, but not for their transport to the PM.