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

  1. Dawei Wang
  2. Zuodong Ye
  3. Wenjie Wei
  4. Jingting Yu
  5. Lihong Huang
  6. Hongmin Zhang
  7. Jianbo Yue  Is a corresponding author
  1. City University of Hong Kong, China
  2. Southern University of Science and Technology, China

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.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Dawei Wang

    City University of Hong Kong, Hong Kong, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7868-775X
  2. Zuodong Ye

    City University of Hong Kong, Hong Kong, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Wenjie Wei

    Southern University of Science and Technology, Shenzhen, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Jingting Yu

    City University of Hong Kong, Shenzhen, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2631-8434
  5. Lihong Huang

    City University of Hong Kong, Hong Kong, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Hongmin Zhang

    Southern University of Science and Technology, Shenzhen, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4356-3615
  7. Jianbo Yue

    Department of Biomedical science, City University of Hong Kong, Hongkong, China
    For correspondence
    jianbyue@cityu.edu.hk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6384-5447

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

  1. Mahak Sharma, Indian Institute of Science Education and Research Mohali, India

Version history

  1. Received: December 18, 2020
  2. Accepted: November 18, 2021
  3. Accepted Manuscript published: November 19, 2021 (version 1)
  4. 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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  1. Dawei Wang
  2. Zuodong Ye
  3. Wenjie Wei
  4. Jingting Yu
  5. Lihong Huang
  6. Hongmin Zhang
  7. Jianbo Yue
(2021)
Capping protein regulates endosomal trafficking by controlling F-actin density around endocytic vesicles and recruiting RAB5 effectors
eLife 10:e65910.
https://doi.org/10.7554/eLife.65910

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