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将V-ATPase招募到ER退出站点,将COPII介导的运输切换到 lysosomal 降解

Yiwei Sun¹, Xi'e Wang², Xiaotong Yang¹

¹National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.

Developmental cell

|November 3, 2023

概括

错误折叠的α1-抗素会在ER退出部位触发一种新的ER-phagy通路. 这一过程涉及V-ATPase和ATG16L1,导致有毒蛋白质聚合物通过溶酶体降解.

科学领域:

细胞生物学细胞生物学
分子生物学分子生物学
自学研究自学研究

背景情况:

细胞内膜网膜 (ER) - 对于通过 lysosomal 降解来维持 ER 稳态至关重要.
精确的ER-phagy启动机制在很大程度上是未知的.
功能障碍的ER平衡与各种疾病有关.

研究的目的:

为了阐明ER-phagy的启动机制.
确定规范ER质量控制的新途径.
研究Z-alpha1-antitrypsin在ER-phagy中的作用.

主要方法:

研究了Z-alpha1-antitrypsin (Z-AAT) 在诱导ER-phagy中的作用.
利用技术研究ER退出站点 (ERES) 和COPII介导的运输.
研究了V-ATPase,ATG16L1和LC3C在ER-phagy诱导中的招募.
评估了FAM134B-II在ER-phagy通路中的作用.

主要成果:

一种致病突变物Z-AAT在ERES中诱导非正规的ER-phagy.
累积的Z-AAT破坏了COPII介导的传输,保留了V0子单元,并在ERES组装了V-ATPase.
V-ATPase招募ATG16L1,导致LC3C脂化,随后招募FAM134B-II.
这种V-ATPase-ATG16L1-LC3C轴 (EVAC) 调解了Z-AAT降解的ER-phagy.
阻断ER出口也激活了这个EVAC路径.

结论:

发现了一种用于ER质量控制的新途径,该途径将COPII介导的传输切换为溶酶体降解.
确定了V-ATPase-ATG16L1-LC3C轴作为ER-phagy启动的关键媒介.
证明Z-AAT诱导的ER-phagy提供了一种清除 ER 中错误折叠的蛋白质的机制.

关键词:

在ATG16L1中使用.COPIIII COPIIII 这是一个很大的问题.在ER退出站点.这是ER-phagy.在 LC3CC 中.第二十四章C 节这是一个V-ATPase.自自是自的过程.蛋白质质量控制蛋白质质量控制 α1 抗素是一种抗素.

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