trim-21 promotes proteasomal degradation of CED-1 for apoptotic cell clearance in C. elegans

  1. Lei Yuan
  2. Peiyao Li
  3. Huiru Jing
  4. Qian Zheng
  5. Hui Xiao  Is a corresponding author
  1. Shaanxi Normal University, China

Abstract

The phagocytic receptor CED-1 mediates apoptotic cell recognition by phagocytic cells, enabling cell corpse clearance in Caenorhabditis elegans. Whether appropriate levels of CED-1 are maintained for executing the engulfment function remains unknown. Here, we identified the C. elegans E3 ubiquitin ligase tripartite motif containing-21 (TRIM-21) as a component of the CED-1 pathway for apoptotic cell clearance. When the NPXY motif of CED-1 was bound to the adaptor protein CED-6 or the YXXL motif of CED-1 was phosphorylated by tyrosine kinase SRC-1 and subsequently bound to the adaptor protein NCK-1 containing the SH2 domain, TRIM-21 functioned in conjunction with UBC-21 to catalyze K48-linked poly-ubiquitination on CED-1, targeting it for proteasomal degradation. In the absence of TRIM-21, CED-1 accumulated post-translationally and drove cell corpse degradation defects, as evidenced by direct binding to VHA-10. These findings reveal a unique mechanism for the maintenance of appropriate levels of CED-1 to regulate apoptotic cell clearance.

Data availability

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

Article and author information

Author details

  1. Lei Yuan

    College of Life Sciences, Shaanxi Normal University, Xi'An, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Peiyao Li

    College of Life Sciences, Shaanxi Normal University, Xi'An, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Huiru Jing

    College of Life Sciences, Shaanxi Normal University, Xi'An, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Qian Zheng

    College of Life Sciences, Shaanxi Normal University, Xi'An, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Hui Xiao

    College of Life Sciences, Shaanxi Normal University, Xi'An, China
    For correspondence
    xiaohui20022008@163.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9305-4486

Funding

National Natural Science Foundation of China (91954114)

  • Hui Xiao

National Natural Science Foundation of China (31871387)

  • Hui Xiao

the Innovative Research Team for the Central Universities (GK202001004)

  • Hui Xiao

Natural Science Foundation Youth Project of Shaanxi Province (2022JQ208)

  • Qian Zheng

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Oliver Hobert, Columbia University, Howard Hughes Medical Institute, United States

Publication history

  1. Received: December 16, 2021
  2. Accepted: August 2, 2022
  3. Accepted Manuscript published: August 5, 2022 (version 1)

Copyright

© 2022, Yuan 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. Lei Yuan
  2. Peiyao Li
  3. Huiru Jing
  4. Qian Zheng
  5. Hui Xiao
(2022)
trim-21 promotes proteasomal degradation of CED-1 for apoptotic cell clearance in C. elegans
eLife 11:e76436.
https://doi.org/10.7554/eLife.76436

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