AUTHOR=Wang Xiaoling , Cheng Shaoyun , Chen Xiangyu , Zhang Wei , Xie Yuxiang , Liu Wanling , You Yanmin , Yi Cun , Zhu Bingkuan , Gu Mengjie , Xu Bin , Lu Yan , Wang Jipeng , Hu Wei 

TITLE=A metabotropic glutamate receptor affects the growth and development of Schistosoma japonicum

JOURNAL=Frontiers in Microbiology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.1045490

DOI=10.3389/fmicb.2022.1045490

ISSN=1664-302X

ABSTRACT=<p>Schistosomiasis is a zoonotic parasitic disease caused by schistosome infection that severely threatens human health. Therapy relies mainly on single drug treatment with praziquantel. Therefore, there is an urgent need to develop alternative medicines. The glutamate neurotransmitter in helminths is involved in many physiological functions by interacting with various cell-surface receptors. However, the roles and detailed regulatory mechanisms of the metabotropic glutamate receptor (mGluR) in the growth and development of <italic>Schistosoma japonicum</italic> remain poorly understood. In this study, we identified two putative mGluRs in <italic>S. japonicum</italic> and named them <italic>Sj</italic>GRM7 (Sjc_001309, similar to GRM7) and <italic>Sj</italic>GRM (Sjc_001163, similar to mGluR). Further validation using a calcium mobilization assay showed that <italic>Sj</italic>GRM7 and <italic>Sj</italic>GRM are glutamate-specific. The results of <italic>in situ</italic> hybridization showed that <italic>Sj</italic>GRM is mainly located in the nerves of both males and gonads of females, and <italic>Sj</italic>GRM7 is principally found in the nerves and gonads of males and females. In a RNA interference experiment, the results showed that <italic>Sj</italic>GRM7 knockdown by double-stranded RNA (dsRNA) in <italic>S. japonicum</italic> caused edema, chassis detachment, and separation of paired worms <italic>in vitro</italic>. Furthermore, dsRNA interference of <italic>Sj</italic>GRM7 could significantly affect the development and egg production of male and female worms <italic>in vivo</italic> and alleviate the host liver granulomas and fibrosis. Finally, we examined the molecular mechanisms underlying the regulatory function of mGluR using RNA sequencing. The data suggest that <italic>Sj</italic>GRM7 propagates its signals through the G protein-coupled receptor signaling pathway to promote nervous system development in <italic>S. japonicum</italic>. In conclusion, <italic>Sj</italic>GRM7 is a potential target for anti-schistosomiasis. This study enables future research on the mechanisms of action of <italic>Schistosomiasis japonica</italic> drugs.</p>