中国病毒学2023，Issue(1) ：9-22.

Domesticated HERV-W env contributes to the activation of the small conductance Ca2+-activated K+type 2 channels via decreased 5-HT4 receptor in recent-onset schizophrenia

Xiulin Wu Qiujin Yan Lianzhong Liu Xing Xue Wei Yao Xuhang Li Wenshi Li Shuang Ding Yaru Xia Dongyan Zhang Fan Zhu
中国病毒学2023，Issue(1) ：9-22.
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Domesticated HERV-W env contributes to the activation of the small conductance Ca2+-activated K+type 2 channels via decreased 5-HT4 receptor in recent-onset schizophrenia

Xiulin Wu 1Qiujin Yan 1Lianzhong Liu 2Xing Xue 1Wei Yao 1Xuhang Li 1Wenshi Li 1Shuang Ding 1Yaru Xia 1Dongyan Zhang 1Fan Zhu3
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作者信息

  • 1. State Key Laboratory of Virology and Department of Medical Microbiology,School of Basic Medical Sciences,Wuhan University,Wuhan,430071,China
  • 2. Wuhan Mental Health Center,Wuhan,430071,China
  • 3. State Key Laboratory of Virology and Department of Medical Microbiology,School of Basic Medical Sciences,Wuhan University,Wuhan,430071,China;Hubei Province Key Laboratory of Allergy&Immunology,Wuhan University,Wuhan,430071,China
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Abstract

The human endogenous retroviruses type W family envelope(HERV-W env)gene is located on chromosome 7q21-22.Our previous studies show that HERV-W env is elevated in schizophrenia and HERV-W env can increase cal-cium influx.Additionally,the 5-HTergic system and particularly 5-hydroxytryptamine(5-HT)receptors play a prominent role in the pathogenesis and treatment of schizophrenia.5-hydroxytryptamine receptor 4(5-HT4R)agonist can block calcium channels.However,the underlying relationship between HERV-W env and 5-HT4R in the etiology of schizophrenia has not been revealed.Here,we used enzyme-linked immunosorbent assay to detect the concentration of HERV-W env and 5-HT4R in the plasma of patients with schizophrenia and we found that there were decreased levels of 5-HT4R and a negative correlation between 5-HT4R and HERV-W env in schizophrenia.Overexpression of HERV-W env decreased the transcription and protein levels of 5-HT4R but increased small conductance Ca2+-activated K+type 2 channels(SK2)expression levels.Further studies revealed that HERV-W env could interact with 5-HT4R.Additionally,luciferase assay showed that an essential region(-364 to-176 from the transcription start site)in the SK2 promoter was required for HERV-W env-induced SK2 expression.Importantly,5-HT4R participated in the regulation of SK2 expression and promoter activity.Electrophysiological recordings suggested that HERV-W env could increase SK2 channel currents and the increase of SK2 currents was inhibited by 5-HT4R.In conclusion,HERV-W env could activate SK2 channels via decreased 5-HT4R,which might exhibit a novel mechanism for HERV-W env to influence neuronal activity in schizophrenia.

Key words

Human endogenous retroviruses type W/(HERV-W)/Env/Small conductance Ca2+-activated K+type 2/channels(SK2)/5-Hydroxytryptamine receptor 4(5-HT4R)/Schizophrenia

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基金项目

National Natural Science Foundation of China(81971943)

National Natural Science Foundation of China(81772196)

National Natural Science Foundation of China(31470264)

National Natural Science Foundation of China(81271820)

National Natural Science Foundation of China(30870789)

National Natural Science Foundation of China(30300117)

Stanley Foundation from the Stanley Medical Research Institute(SMRI),United States(06R-1366)

Medicine Research Center for Structural Biology of Wuhan University for providing the confocal microscopy(Leica-LCS-SP8-STED)

出版年

2023
中国病毒学
中国科学院武汉病毒研究所，中国微生物学会

中国病毒学

CSTPCDCSCD北大核心
影响因子：0.393
ISSN：1674-0769
参考文献量91
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