The Golgi stacking protein GORASP2/GRASP55 serves as an energy sensor to promote autophagosome maturation under glucose starvation.
The Golgi stacking protein GORASP2/GRASP55 serves as an energy sensor to promote autophagosome maturation under glucose starvation.
复制标题
高尔基体堆积蛋白 GORASP2/GRASP55 作为能量传感器，在葡萄糖饥饿下促进自噬体成熟。
DOI：
10.1080/15548627.2018.1491214
复制
发表时间：
2018
期刊：
影响因子：
13.3
通讯作者：
Wang,Yanzhuang
中科院分区：
文献类型：
--
作者：
Zhang,Xiaoyan;Wang,Yanzhuang
高尔基体是细胞内分泌途径的中心细胞器。高尔基体独特的堆叠结构的形成确保了蛋白质的准确糖基化和分选。然而，高尔基体的结构和功能如何对细胞外压力做出反应在很大程度上还没有被探索。在最近的一项研究中，我们报道了在短期缺糖条件下，高尔基体堆积蛋白GORASP2/GRASP55的一个亚群被靶向从高尔基体到自噬小体和溶酶体之间的界面，以促进自噬体成熟；这一过程受O-GlcN酰化调控。在生长条件下，GORASP2是O-GlcN酰化的，在高尔基体中作为堆积蛋白发挥作用。在葡萄糖饥饿时，GORASP2被去O-GlcN酰化，并部分从高尔基体重新定位到自噬小体-溶酶体界面上，在那里它与自噬小体上的脂化的LC3和溶酶体上的LAMP2相互作用，并作为膜纽带促进自噬小体-溶酶体的融合。因此，我们的研究发现高尔基体胶蛋白在自噬中扮演了一个非常规的角色，这种作用是通过感知血糖水平来实现的。
The Golgi apparatus is a central intracellular membrane organelle in the secretory pathway. The formation of the unique stacked architecture of the Golgi ensures accurate protein glycosylation and sorting. However, how the Golgi structure and function respond to extracellular stresses is largely unexplored. In a recent study, we reported that under short-term glucose deprivation, a subpopulation of the Golgi stacking protein GORASP2/GRASP55 is targeted from the Golgi to the interface between autophagosomes and lysosomes to promote autophagosome maturation; this process is regulated by O-GlcNAcylation. Under growth condition, GORASP2 is O-GlcNAcylated and functions as a stacking protein in the Golgi. Upon glucose starvation, GORASP2 is de-O-GlcNAcylated and is partially relocated from the Golgi to the autophagosome-lysosome interface, where it interacts with lipidated LC3 on autophagosomes and LAMP2 on lysosomes, and functions as a membrane tether to facilitate autophagosome-lysosome fusion. Therefore, our study uncovered an unconventional role of the Golgi ‘glue’ protein in autophagy that acts by sensing the glucose level.