溶酶体
内体
自噬
细胞生物学
效应器
生物
脂质双层融合
TFEB
小型GTPase
内吞作用
液泡
自噬体
内吞循环
细胞器
高尔基体
蛋白质降解
分泌物
信号转导
细胞内
生物化学
酶
细胞凋亡
膜
作者
Ruxiao Xing,Hejiang Zhou,Youli Jian,Lingling Li,Min Wang,Nan Liu,Qiuyuan Yin,Ziqi Liang,Weixiang Guo,Chonglin Yang
标识
DOI:10.1083/jcb.202007061
摘要
The effectors of the Rab7 small GTPase play multiple roles in Rab7-dependent endosome-lysosome and autophagy-lysosome pathways. However, it is largely unknown how distinct Rab7 effectors coordinate to maintain the homeostasis of late endosomes and lysosomes to ensure appropriate endolysosomal and autolysosomal degradation. Here we report that WDR91, a Rab7 effector required for early-to-late endosome conversion, is essential for lysosome function and homeostasis. Mice lacking Wdr91 specifically in the central nervous system exhibited behavioral defects and marked neuronal loss in the cerebral and cerebellar cortices. At the cellular level, WDR91 deficiency causes PtdIns3P-independent enlargement and dysfunction of lysosomes, leading to accumulation of autophagic cargoes in mouse neurons. WDR91 competes with the VPS41 subunit of the HOPS complex, another Rab7 effector, for binding to Rab7, thereby facilitating Rab7-dependent lysosome fusion in a controlled manner. WDR91 thus maintains an appropriate level of lysosome fusion to guard the normal function and survival of neurons.
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