Inner membrane complex proteomics reveals a palmitoylation regulation critical for intraerythrocytic development of malaria parasite

  1. Pengge Qian
  2. Xu Wang
  3. Chuan-Qi Zhong
  4. Jiaxu Wang
  5. Mengya Cai
  6. Wang Nguitragool
  7. Jian Li  Is a corresponding author
  8. Huiting Cui  Is a corresponding author
  9. Jing Yuan  Is a corresponding author
  1. Xiamen University, China
  2. Xiamen Center for Disease Control and Prevention, China
  3. Mahidol University, Thailand

Abstract

Malaria is caused by infection of the erythrocytes by the parasites Plasmodium. Inside the erythrocytes, the parasites multiply via schizogony, an unconventional cell division mode. The Inner Membrane Complex (IMC), an organelle located beneath the parasite plasma membrane, serving as the platform for protein anchorage, is essential for schizogony. So far, complete repertoire of IMC proteins and their localization determinants remain unclear. Here we used biotin ligase (TurboID)-based proximity labelling to compile the proteome of the schizont IMC of rodent malaria parasite Plasmodium yoelii. In total, 300 TurboID-interacting proteins were identified. 18 of 21 selected candidates were confirmed to localize in the IMC, indicating good reliability. In light of the existing palmitome of Plasmodium falciparum, 83 proteins of the P. yoelii IMC proteome are potentially palmitoylated. We further identified DHHC2 as the major resident palmitoyl-acyl-transferase of the IMC. Depletion of DHHC2 led to defective schizont segmentation and growth arrest both in vitro and in vivo. DHHC2 was found to palmitoylate two critical IMC proteins CDPK1 and GAP45 for their IMC localization. In summary, this study reports an inventory of new IMC proteins and demonstrates a central role of DHHC2 in governing IMC localization of proteins during the schizont development.

Data availability

The Mass spectrometry proteomic data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the data identifier PXD028193. All other relevant data in this study are submitted as supplementary source files.

The following data sets were generated

Article and author information

Author details

  1. Pengge Qian

    Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Xu Wang

    Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Chuan-Qi Zhong

    Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Jiaxu Wang

    Xiamen Center for Disease Control and Prevention, Xiamen, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Mengya Cai

    Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Wang Nguitragool

    Department of Molecular Tropical Medicine and Genetics, Mahidol University, Bangkok, Thailand
    Competing interests
    The authors declare that no competing interests exist.
  7. Jian Li

    Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, China
    For correspondence
    jianli_204@xmu.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
  8. Huiting Cui

    Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, China
    For correspondence
    cuihuiting@xmu.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
  9. Jing Yuan

    Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, China
    For correspondence
    yuanjing@xmu.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8907-9143

Funding

National Natural Science Foundation of China (32170427,31970387,31872214)

  • Jing Yuan

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

Reviewing Editor

  1. Olivier Silvie, Sorbonne Université, UPMC Univ Paris 06, INSERM, CNRS, France

Ethics

Animal experimentation: All mouse experiments were performed by approved protocols (XMULAC20140004) by the Committee for Care and Use of Laboratory Animals of Xiamen University. The ICR mice (female, 5 to 6 weeks old) were purchased from the Animal Care Center of Xiamen University

Version history

  1. Preprint posted: January 29, 2022 (view preprint)
  2. Received: January 29, 2022
  3. Accepted: June 24, 2022
  4. Accepted Manuscript published: July 1, 2022 (version 1)
  5. Accepted Manuscript updated: July 4, 2022 (version 2)
  6. Version of Record published: July 18, 2022 (version 3)

Copyright

© 2022, Qian 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. Pengge Qian
  2. Xu Wang
  3. Chuan-Qi Zhong
  4. Jiaxu Wang
  5. Mengya Cai
  6. Wang Nguitragool
  7. Jian Li
  8. Huiting Cui
  9. Jing Yuan
(2022)
Inner membrane complex proteomics reveals a palmitoylation regulation critical for intraerythrocytic development of malaria parasite
eLife 11:e77447.
https://doi.org/10.7554/eLife.77447

Share this article

https://doi.org/10.7554/eLife.77447

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