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UNC-43/CaMKII-triggered anterograde signals recruit GABAARs to mediate inhibitory synaptic transmission and plasticity at C. elegans NMJs

Author

Listed:
  • Yue Hao

    (ShanghaiTech University
    CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Haowen Liu

    (The University of Queensland)

  • Xian-Ting Zeng

    (ShanghaiTech University)

  • Ya Wang

    (Huazhong University of Science and Technology)

  • Wan-Xin Zeng

    (ShanghaiTech University
    CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Kang-Ying Qian

    (ShanghaiTech University
    CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Lei Li

    (The University of Queensland)

  • Ming-Xuan Chi

    (ShanghaiTech University)

  • Shangbang Gao

    (Huazhong University of Science and Technology)

  • Zhitao Hu

    (The University of Queensland)

  • Xia-Jing Tong

    (ShanghaiTech University)

Abstract

Disturbed inhibitory synaptic transmission has functional impacts on neurodevelopmental and psychiatric disorders. An essential mechanism for modulating inhibitory synaptic transmission is alteration of the postsynaptic abundance of GABAARs, which are stabilized by postsynaptic scaffold proteins and recruited by presynaptic signals. However, how GABAergic neurons trigger signals to transsynaptically recruit GABAARs remains elusive. Here, we show that UNC-43/CaMKII functions at GABAergic neurons to recruit GABAARs and modulate inhibitory synaptic transmission at C. elegans neuromuscular junctions. We demonstrate that UNC-43 promotes presynaptic MADD-4B/Punctin secretion and NRX-1α/Neurexin surface delivery. Together, MADD-4B and NRX-1α recruit postsynaptic NLG-1/Neuroligin and stabilize GABAARs. Further, the excitation of GABAergic neurons potentiates the recruitment of NLG-1-stabilized-GABAARs, which depends on UNC-43, MADD-4B, and NRX-1. These data all support that UNC-43 triggers MADD-4B and NRX-1α, which act as anterograde signals to recruit postsynaptic GABAARs. Thus, our findings elucidate a mechanism for pre- and postsynaptic communication and inhibitory synaptic transmission and plasticity.

Suggested Citation

  • Yue Hao & Haowen Liu & Xian-Ting Zeng & Ya Wang & Wan-Xin Zeng & Kang-Ying Qian & Lei Li & Ming-Xuan Chi & Shangbang Gao & Zhitao Hu & Xia-Jing Tong, 2023. "UNC-43/CaMKII-triggered anterograde signals recruit GABAARs to mediate inhibitory synaptic transmission and plasticity at C. elegans NMJs," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37137-0
    DOI: 10.1038/s41467-023-37137-0
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    References listed on IDEAS

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