Roles of endosomal phosphoinositides in intracellular trafficking

内溶酶体运输是一个严格调控的过程，涉及膜融合和分裂事件，其确保内体、溶酶体和其他细胞内细胞器或囊泡内货物的适当递送和交换。它是几种细胞功能所必需的，如蛋白质和脂质转运、自噬和溶酶体中大分子的降解。它是如何调节的是细胞生物学中的一个基本问题。我们的研究计划打算使用病毒作为手段来监测和了解细胞中的囊泡运输。事实上，病毒已经进化出利用甚至调节内体成熟或内溶酶体运输的机制，因为它可以决定感染是否成功。因此，它们可以代表用于研究细胞贩运途径的强大和宝贵的工具。我们发现Vac 14/Fig 4/PIKfyve复合物的蛋白质，其调节磷脂酰肌醇（3，5）二磷酸在溶酶体内膜的合成，是埃博拉病毒（EboV）和严重急性呼吸综合征冠状病毒（SARS-CoV）感染所必需的。合成PI（3，5）P2的酶复合物如何被激活以及PI（3，5）P2在内溶酶体运输中的作用仍不清楚。在这里，我们建议使用EboV和SARS-CoV来回答这些问题。

Endolysosomal trafficking is a tightly regulated process that involves membrane fusion and fission events, which ensure proper delivery and exchange of cargoes within endosomes, lysosomes, and other intracellular organelles or vesicles. It is essential for several cellular functions such as protein and lipid transport, autophagy, and degradation of macromolecules in lysosomes. How it is regulated is a fundamental issue in cellular biology. Our research program intends to use viruses as means to monitor and understand vesicular trafficking in cells. Indeed, viruses have evolved mechanisms to use and even regulate endosomal maturation or endolysosomal trafficking, since it can determine whether the infection is successful or not. Therefore, they can represent powerful and invaluable tools for the study of cellular trafficking pathways. We found that proteins of the Vac14/Fig4/PIKfyve complex, which regulates the synthesis of the phosphoinositide(3,5)bisphosphate at the endolysosomal membrane, are essential for infection by Ebola virus (EboV) and severe acute respiratory syndrome coronavirus (SARS-CoV). How the enzymatic complex synthesizing PI(3,5)P2 is activated and the role of PI(3,5)P2 in endolysosomal trafficking remain unclear. Here, we propose to use EboV and SARS-CoV to answer these questions.