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Neurexins regulate presynaptic GABAB-receptors at central synapses

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Listed:
  • Fujun Luo

    (Stanford University Medical School
    Bioland Laboratory (Guangzhou Regenerative Medicine and Health-Guangdong Laboratory))

  • Alessandra Sclip

    (Stanford University Medical School)

  • Sean Merrill

    (Stanford University Medical School)

  • Thomas C. Südhof

    (Stanford University Medical School)

Abstract

Diverse signaling complexes are precisely assembled at the presynaptic active zone for dynamic modulation of synaptic transmission and synaptic plasticity. Presynaptic GABAB-receptors nucleate critical signaling complexes regulating neurotransmitter release at most synapses. However, the molecular mechanisms underlying assembly of GABAB-receptor signaling complexes remain unclear. Here we show that neurexins are required for the localization and function of presynaptic GABAB-receptor signaling complexes. At four model synapses, excitatory calyx of Held synapses in the brainstem, excitatory and inhibitory synapses on hippocampal CA1-region pyramidal neurons, and inhibitory basket cell synapses in the cerebellum, deletion of neurexins rendered neurotransmitter release significantly less sensitive to GABAB-receptor activation. Moreover, deletion of neurexins caused a loss of GABAB-receptors from the presynaptic active zone of the calyx synapse. These findings extend the role of neurexins at the presynaptic active zone to enabling GABAB-receptor signaling, supporting the notion that neurexins function as central organizers of active zone signaling complexes.

Suggested Citation

  • Fujun Luo & Alessandra Sclip & Sean Merrill & Thomas C. Südhof, 2021. "Neurexins regulate presynaptic GABAB-receptors at central synapses," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22753-5
    DOI: 10.1038/s41467-021-22753-5
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    Cited by:

    1. 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.
    2. Xuchen Zhang & Pei-Yi Lin & Kif Liakath-Ali & Thomas C. Südhof, 2022. "Teneurins assemble into presynaptic nanoclusters that promote synapse formation via postsynaptic non-teneurin ligands," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

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