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Postsynaptic RIM1 modulates synaptic function by facilitating membrane delivery of recycling NMDARs in hippocampal neurons

Author

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  • Jiejie Wang

    (NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou)

  • Xinyou Lv

    (NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou)

  • Yu Wu

    (NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou)

  • Tao Xu

    (NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou)

  • Mingfei Jiao

    (NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou)

  • Risheng Yang

    (Fourth Military Medical University)

  • Xia Li

    (Fourth Military Medical University)

  • Ming Chen

    (NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou)

  • Yinggang Yan

    (NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou)

  • Changwan Chen

    (NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou)

  • Weifan Dong

    (NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou)

  • Wei Yang

    (NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou)

  • Min Zhuo

    (Frontier Institutes of Life Science, Science and Technology, Xi’an Jiaotong University
    Faculty of Medicine, University of Toronto)

  • Tao Chen

    (Fourth Military Medical University
    Frontier Institutes of Life Science, Science and Technology, Xi’an Jiaotong University)

  • Jianhong Luo

    (NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou)

  • Shuang Qiu

    (NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou
    Second Affiliated Hospital, Zhejiang University School of Medicine)

Abstract

NMDA receptors (NMDARs) are crucial for excitatory synaptic transmission and synaptic plasticity. The number and subunit composition of synaptic NMDARs are tightly controlled by neuronal activity and sensory experience, but the molecular mechanism mediating NMDAR trafficking remains poorly understood. Here, we report that RIM1, with a well-established role in presynaptic vesicle release, also localizes postsynaptically in the mouse hippocampus. Postsynaptic RIM1 in hippocampal CA1 region is required for basal NMDAR-, but not AMPA receptor (AMPAR)-, mediated synaptic responses, and contributes to synaptic plasticity and hippocampus-dependent memory. Moreover, RIM1 levels in hippocampal neurons influence both the constitutive and regulated NMDAR trafficking, without affecting constitutive AMPAR trafficking. We further demonstrate that RIM1 binds to Rab11 via its N terminus, and knockdown of RIM1 impairs membrane insertion of Rab11-positive recycling endosomes containing NMDARs. Together, these results identify a RIM1-dependent mechanism critical for modulating synaptic function by facilitating membrane delivery of recycling NMDARs.

Suggested Citation

  • Jiejie Wang & Xinyou Lv & Yu Wu & Tao Xu & Mingfei Jiao & Risheng Yang & Xia Li & Ming Chen & Yinggang Yan & Changwan Chen & Weifan Dong & Wei Yang & Min Zhuo & Tao Chen & Jianhong Luo & Shuang Qiu, 2018. "Postsynaptic RIM1 modulates synaptic function by facilitating membrane delivery of recycling NMDARs in hippocampal neurons," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04672-0
    DOI: 10.1038/s41467-018-04672-0
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    Cited by:

    1. Huan Sheng & Chao Lei & Yu Yuan & Yali Fu & Dongyang Cui & Li Yang & Da Shao & Zixuan Cao & Hao Yang & Xinli Guo & Chenshan Chu & Yaxian Wen & Zhangyin Cai & Ming Chen & Bin Lai & Ping Zheng, 2023. "Nucleus accumbens circuit disinhibits lateral hypothalamus glutamatergic neurons contributing to morphine withdrawal memory in male mice," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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