The autophagic membrane tether ATG2A transfers lipids between membranes
The autophagic membrane tether ATG2A transfers lipids between membranes
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DOI：
10.7554/elife.45777
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发表时间：
2019-07-04
期刊：
影响因子：
7.7
通讯作者：
Otomo, Takanori
中科院分区：
文献类型：
--
作者：
Maeda, Shintaro;Otomo, Chinatsu;Otomo, Takanori
自噬体膜室从头形成的一个神秘步骤是前体膜吞噬细胞的扩张，这需要获得脂质作为构建块。自噬相关蛋白2 （Autophagy-related 2, ATG2）是一种杆状蛋白，可将富含磷脂酰肌醇3-磷酸（PI3P）的吞噬细胞连接到内质网（ER），被认为是吞噬细胞扩张所必需的，但其潜在机制尚不清楚。在这里，我们证明了人类ATG2A是一种脂质转移蛋白。ATG2A可以从膜囊泡中提取脂质并将其卸载到其他囊泡中。ATG2A在栓系囊泡之间的脂质转移比在非栓系囊泡之间更有效。PI3P效应物WIPI4和WIPI1将ATG2A稳定地结合到含PI3P的囊泡上，从而促进了ATG2A介导的含PI3P囊泡和不含PI3P囊泡之间的系固和脂质转移。基于这些结果，我们提出atg2介导的脂质从内质网转移到吞噬细胞使吞噬细胞扩张。
An enigmatic step in de novo formation of the autophagosome membrane compartment is the expansion of the precursor membrane phagophore, which requires the acquisition of lipids to serve as building blocks. Autophagy-related 2 (ATG2), the rod-shaped protein that tethers phosphatidylinositol 3-phosphate (PI3P)-enriched phagophores to the endoplasmic reticulum (ER), is suggested to be essential for phagophore expansion, but the underlying mechanism remains unclear. Here, we demonstrate that human ATG2A is a lipid transfer protein. ATG2A can extract lipids from membrane vesicles and unload them to other vesicles. Lipid transfer by ATG2A is more efficient between tethered vesicles than between untethered vesicles. The PI3P effectors WIPI4 and WIPI1 associate ATG2A stably to PI3P-containing vesicles, thereby facilitating ATG2A-mediated tethering and lipid transfer between PI3P-containing vesicles and PI3P-free vesicles. Based on these results, we propose that ATG2-mediated transfer of lipids from the ER to the phagophore enables phagophore expansion.