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

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 en...

Full description

Bibliographic Details
Main Authors: Dawei Wang, Zuodong Ye, Wenjie Wei, Jingting Yu, Lihong Huang, Hongmin Zhang, Jianbo Yue
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2021-11-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/65910
_version_ 1811180473113640960
author Dawei Wang
Zuodong Ye
Wenjie Wei
Jingting Yu
Lihong Huang
Hongmin Zhang
Jianbo Yue
author_facet Dawei Wang
Zuodong Ye
Wenjie Wei
Jingting Yu
Lihong Huang
Hongmin Zhang
Jianbo Yue
author_sort Dawei Wang
collection DOAJ
description 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.
first_indexed 2024-04-11T09:03:41Z
format Article
id doaj.art-47da48c69a5e46f49d024ae0ed8bc565
institution Directory Open Access Journal
issn 2050-084X
language English
last_indexed 2024-04-11T09:03:41Z
publishDate 2021-11-01
publisher eLife Sciences Publications Ltd
record_format Article
series eLife
spelling doaj.art-47da48c69a5e46f49d024ae0ed8bc5652022-12-22T04:32:42ZengeLife Sciences Publications LtdeLife2050-084X2021-11-011010.7554/eLife.65910Capping protein regulates endosomal trafficking by controlling F-actin density around endocytic vesicles and recruiting RAB5 effectorsDawei Wang0https://orcid.org/0000-0002-7868-775XZuodong Ye1Wenjie Wei2Jingting Yu3https://orcid.org/0000-0002-2631-8434Lihong Huang4Hongmin Zhang5https://orcid.org/0000-0003-4356-3615Jianbo Yue6https://orcid.org/0000-0001-6384-5447City University of Hong Kong Shenzhen Research Institute, Shenzhen, China; Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, ChinaCity University of Hong Kong Shenzhen Research Institute, Shenzhen, China; Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, ChinaCore Research Facilities, Southern University of Science and Technology, Shenzhen, ChinaCity University of Hong Kong Shenzhen Research Institute, Shenzhen, ChinaCity University of Hong Kong Shenzhen Research Institute, Shenzhen, China; Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, ChinaDepartment 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, ChinaCity 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, ChinaActin 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.https://elifesciences.org/articles/65910CapZF-actinendosomeRAB5endosomal traffickingRabaptin-5
spellingShingle Dawei Wang
Zuodong Ye
Wenjie Wei
Jingting Yu
Lihong Huang
Hongmin Zhang
Jianbo Yue
Capping protein regulates endosomal trafficking by controlling F-actin density around endocytic vesicles and recruiting RAB5 effectors
eLife
CapZ
F-actin
endosome
RAB5
endosomal trafficking
Rabaptin-5
title Capping protein regulates endosomal trafficking by controlling F-actin density around endocytic vesicles and recruiting RAB5 effectors
title_full Capping protein regulates endosomal trafficking by controlling F-actin density around endocytic vesicles and recruiting RAB5 effectors
title_fullStr Capping protein regulates endosomal trafficking by controlling F-actin density around endocytic vesicles and recruiting RAB5 effectors
title_full_unstemmed Capping protein regulates endosomal trafficking by controlling F-actin density around endocytic vesicles and recruiting RAB5 effectors
title_short Capping protein regulates endosomal trafficking by controlling F-actin density around endocytic vesicles and recruiting RAB5 effectors
title_sort capping protein regulates endosomal trafficking by controlling f actin density around endocytic vesicles and recruiting rab5 effectors
topic CapZ
F-actin
endosome
RAB5
endosomal trafficking
Rabaptin-5
url https://elifesciences.org/articles/65910
work_keys_str_mv AT daweiwang cappingproteinregulatesendosomaltraffickingbycontrollingfactindensityaroundendocyticvesiclesandrecruitingrab5effectors
AT zuodongye cappingproteinregulatesendosomaltraffickingbycontrollingfactindensityaroundendocyticvesiclesandrecruitingrab5effectors
AT wenjiewei cappingproteinregulatesendosomaltraffickingbycontrollingfactindensityaroundendocyticvesiclesandrecruitingrab5effectors
AT jingtingyu cappingproteinregulatesendosomaltraffickingbycontrollingfactindensityaroundendocyticvesiclesandrecruitingrab5effectors
AT lihonghuang cappingproteinregulatesendosomaltraffickingbycontrollingfactindensityaroundendocyticvesiclesandrecruitingrab5effectors
AT hongminzhang cappingproteinregulatesendosomaltraffickingbycontrollingfactindensityaroundendocyticvesiclesandrecruitingrab5effectors
AT jianboyue cappingproteinregulatesendosomaltraffickingbycontrollingfactindensityaroundendocyticvesiclesandrecruitingrab5effectors