City University of Hong Kong Shenzhen Research Institute, Shenzhen, China; Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China
Zuodong Ye
City University of Hong Kong Shenzhen Research Institute, Shenzhen, China; Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China
Wenjie Wei
Core Research Facilities, Southern University of Science and Technology, Shenzhen, China
City University of Hong Kong Shenzhen Research Institute, Shenzhen, China
Lihong Huang
City University of Hong Kong Shenzhen Research Institute, Shenzhen, China; Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, 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
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
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.
