Capping protein regulates endosomal trafficking by controlling F-actin density around endocytic vesicles and recruiting RAB5 effectors
Abstract
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 a 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, 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.
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All data generated or analysed during this study are included in the manuscript and supporting files.
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Funding
Research Grants Council, University Grants Committee (11101717)
- Jianbo Yue
Research Grants Council, University Grants Committee (11103620)
- Jianbo Yue
National Natural Science Foundation of China (21778045)
- Jianbo Yue
National Natural Science Foundation of China (2070702)
- Jianbo Yue
Science, Technology and Innovation Commission of Shenzhen Municipality (JCYJ20160229165235739)
- Jianbo Yue
Science, Technology and Innovation Commission of Shenzhen Municipality (JCYJ20170413141331470)
- Jianbo Yue
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Mahak Sharma, Indian Institute of Science Education and Research Mohali, India
Version history
- Received: December 18, 2020
- Accepted: November 18, 2021
- Accepted Manuscript published: November 19, 2021 (version 1)
- Version of Record published: December 8, 2021 (version 2)
Copyright
© 2021, Wang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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