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An intracellular membrane protein GEP1 regulates xanthurenic acid induced gametogenesis of malaria parasites

Author

Listed:
  • Yuanyuan Jiang

    (Xiamen University)

  • Jun Wei

    (Xiamen University)

  • Huiting Cui

    (Xiamen University)

  • Chuanyuan Liu

    (Xiamen University)

  • Yuan Zhi

    (Xiamen University)

  • ZhengZheng Jiang

    (Xiamen University)

  • Zhenkui Li

    (Xiamen University)

  • Shaoneng Li

    (Xiamen University)

  • Zhenke Yang

    (Xiamen University)

  • Xu Wang

    (Xiamen University)

  • Pengge Qian

    (Xiamen University)

  • Cui Zhang

    (Xiamen University)

  • Chuanqi Zhong

    (Xiamen University)

  • Xin-zhuan Su

    (Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Jing Yuan

    (Xiamen University
    Lingnan Guangdong Laboratory of Modern Agriculture)

Abstract

Gametocytes differentiation to gametes (gametogenesis) within mosquitos is essential for malaria parasite transmission. Both reduction in temperature and mosquito-derived XA or elevated pH are required for triggering cGMP/PKG dependent gametogenesis. However, the parasite molecule for sensing or transducing these environmental signals to initiate gametogenesis remains unknown. Here we perform a CRISPR/Cas9-based functional screening of 59 membrane proteins expressed in the gametocytes of Plasmodium yoelii and identify that GEP1 is required for XA-stimulated gametogenesis. GEP1 disruption abolishes XA-stimulated cGMP synthesis and the subsequent signaling and cellular events, such as Ca2+ mobilization, gamete formation, and gametes egress out of erythrocytes. GEP1 interacts with GCα, a cGMP synthesizing enzyme in gametocytes. Both GEP1 and GCα are expressed in cytoplasmic puncta of both male and female gametocytes. Depletion of GCα impairs XA-stimulated gametogenesis, mimicking the defect of GEP1 disruption. The identification of GEP1 being essential for gametogenesis provides a potential new target for intervention of parasite transmission.

Suggested Citation

  • Yuanyuan Jiang & Jun Wei & Huiting Cui & Chuanyuan Liu & Yuan Zhi & ZhengZheng Jiang & Zhenkui Li & Shaoneng Li & Zhenke Yang & Xu Wang & Pengge Qian & Cui Zhang & Chuanqi Zhong & Xin-zhuan Su & Jing , 2020. "An intracellular membrane protein GEP1 regulates xanthurenic acid induced gametogenesis of malaria parasites," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15479-3
    DOI: 10.1038/s41467-020-15479-3
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    Cited by:

    1. Jiepeng Guan & Peijia Wu & Xiaoli Mo & Xiaolong Zhang & Wenqi Liang & Xiaoming Zhang & Lubin Jiang & Jian Li & Huiting Cui & Jing Yuan, 2024. "An axonemal intron splicing program sustains Plasmodium male development," Nature Communications, Nature, vol. 15(1), pages 1-20, December.

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