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Neurexin-3 subsynaptic densities are spatially distinct from Neurexin-1 and essential for excitatory synapse nanoscale organization in the hippocampus

Author

Listed:
  • Brian A Lloyd

    (University of Colorado Anschutz School of Medicine, Department of Pharmacology)

  • Ying Han

    (Peking University Shenzhen Graduate School
    Shenzhen Bay Laboratory)

  • Rebecca Roth

    (University of Colorado Anschutz School of Medicine, Department of Pharmacology)

  • Bo Zhang

    (Peking University Shenzhen Graduate School
    Shenzhen Bay Laboratory)

  • Jason Aoto

    (University of Colorado Anschutz School of Medicine, Department of Pharmacology)

Abstract

Proteins critical for synaptic transmission are non-uniformly distributed and assembled into regions of high density called subsynaptic densities (SSDs) that transsynaptically align in nanocolumns. Neurexin-1 and neurexin-3 are essential presynaptic adhesion molecules that non-redundantly control NMDAR- and AMPAR-mediated synaptic transmission, respectively, via transsynaptic interactions with distinct postsynaptic ligands. Despite their functional relevance, fundamental questions regarding the nanoscale properties of individual neurexins, their influence on the subsynaptic organization of excitatory synapses and the mechanisms controlling how individual neurexins engage in precise transsynaptic interactions are unknown. Using Double Helix 3D dSTORM and neurexin mouse models, we identify neurexin-3 as a critical presynaptic adhesion molecule that regulates excitatory synapse nano-organization in hippocampus. Furthermore, endogenous neurexin-1 and neurexin-3 form discrete and non-overlapping SSDs that are enriched opposite their postsynaptic ligands. Thus, the nanoscale organization of neurexin-1 and neurexin-3 may explain how individual neurexins signal in parallel to govern different synaptic properties.

Suggested Citation

  • Brian A Lloyd & Ying Han & Rebecca Roth & Bo Zhang & Jason Aoto, 2023. "Neurexin-3 subsynaptic densities are spatially distinct from Neurexin-1 and essential for excitatory synapse nanoscale organization in the hippocampus," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40419-2
    DOI: 10.1038/s41467-023-40419-2
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    References listed on IDEAS

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    4. Justin H. Trotter & Cosmos Yuqi Wang & Peng Zhou & George Nakahara & Thomas C. Südhof, 2023. "A combinatorial code of neurexin-3 alternative splicing controls inhibitory synapses via a trans-synaptic dystroglycan signaling loop," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
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