Capping protein regulates endosomal trafficking by controlling F-actin density around endocytic vesicles and recruiting RAB5 effectors

eLife

Jingting Yu¹  Lihong Huang²  Zuodong Ye²  Dawei Wang²  Jianbo Yue³  Wenjie Wei⁴  Hongmin Zhang⁵ 

[1] City University of Hong Kong Shenzhen Research Institute, Shenzhen, China;City University of Hong Kong Shenzhen Research Institute, Shenzhen, China;Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China;City University of Hong Kong Shenzhen Research Institute, Shenzhen, China;Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China;City University of Hong Kong Chengdu Research Institute, Chengdu, China;Core Research Facilities, Southern University of Science and Technology, Shenzhen, China;Department of Biology, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research and Shenzhen Key Laboratory of Cell Microenvironment, Southern University of Science and Technology, Shenzhen, China;

关键词: CapZ;    F-actin;    endosome;    RAB5;    endosomal trafficking;    Rabaptin-5;    Arp2/3;    Rabex-5;    Human;   

DOI  :  10.7554/eLife.65910

来源: eLife Sciences Publications, Ltd

【 摘 要 】

Actin filaments (F-actin) have been implicated in various steps of endosomal trafficking, and the length of F-actin is controlled by actin capping proteins, such as CapZ, which is a stable heterodimeric protein complex consisting of α and β subunits. However, the role of these capping proteins in endosomal trafficking remains elusive. Here, we found that CapZ docks to endocytic vesicles via its C-terminal actin-binding motif. CapZ knockout significantly increases the F-actin density around immature early endosomes, and this impedes fusion between these vesicles, manifested by the accumulation of small endocytic vesicles in CapZ-knockout cells. CapZ also recruits several RAB5 effectors, such as Rabaptin-5 and Rabex-5, to RAB5-positive early endosomes via its N-terminal domain, and this further activates RAB5. Collectively, our results indicate that CapZ regulates endosomal trafficking by controlling actin density around early endosomes and recruiting RAB5 effectors.

【 授权许可】

CC BY