LET-502/ROCK Regulates Endocytic Recycling by Promoting Activation of RAB-5 in a Distinct Subpopulation of Sorting Endosomes

Cell Reports

卷:32

Shimin Wang¹  Junbo Hu²  Can Hu²  Yuxin Yao²  Zhen He²  Yuhan Liao²  Jun He²  Wenjuan Zhang²  Juan Chen²  Dan Chen²  Chao Yang²  Qian Luo²  Anbing Shi²  Long Lin³  Tian Xia⁴ 

[1] Department of Pathology, Maternal and Child Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430070 Hubei, China;

[2] Department of Biochemistry and Molecular Biology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 Hubei, China;

[3] Department of Informatics Engineering, School of Electronic Information and Communications, Huazhong University of Science and Technology, Wuhan, 430074 Hubei, China;

关键词: C. elegans;    endocytic recycling;    RAB-5/Rab5;    LET-502/ROCK;    CED-10/Rac1;    RABX-5;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: To explore the mechanism of Rab5/RAB-5 activation during endocytic recycling, we perform a genome-wide RNAi screen and identify a recycling regulator, LET-502/ROCK. LET-502 preferentially interacts with RAB-5(GDP) and activates RABX-5 GEF activity toward RAB-5, presumably by disrupting the self-inhibiting conformation of RABX-5. Furthermore, we find that the concomitant loss of LET-502 and another CED-10 effector, TBC-2/RAB-5-GAP, results in an endosomal buildup of RAB-5, indicating that CED-10 directs TBC-2-mediated RAB-5 inactivation and re-activates RAB-5 via LET-502 afterward. Then, we compare the functional position of LET-502 with that of RME-6/RAB-5-GEF. Loss of LET-502-RABX-5 module or RME-6 leads to diminished RAB-5 presence in spatially distinct endosome groups. We conclude that in the intestine of C. elegans, RAB-5 resides in discrete endosome subpopulations. Under the oversight of CED-10, LET-502 synergizes with RABX-5 to revitalize RAB-5 on a subset of endosomes in the deep cytosol, ensuring the progress of basolateral recycling.

【 授权许可】

Unknown