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

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 and Jing Yuan ()
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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

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-15479-3

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