Endosomal sorting protein SNX4 limits synaptic vesicle docking and release

Josse Poppinga, Nolan J. Barrett, L. Niels Cornelisse, Matthijs Verhage, Jan R.T. van Weering

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Sorting nexin 4 (SNX4) is an evolutionary conserved organizer of membrane recycling. In neurons, SNX4 accumulates in synapses, but how SNX4 affects synapse function remains unknown. We generated a conditional SNX4 knock-out mouse model and report that SNX4 cKO synapses show enhanced neurotransmission during train stimulation, while the first evoked EPSC was normal. SNX4 depletion did not affect vesicle recycling, basic autophagic flux, or the levels and localization of SNARE-protein VAMP2/synaptobrevin-2. However, SNX4 depletion affected synapse ultrastructure: an increase in docked synaptic vesicles at the active zone, while the overall vesicle number was normal, and a decreased active zone length. These effects together lead to a substantially increased density of docked vesicles per release site. In conclusion, SNX4 is a negative regulator of synaptic vesicle docking and release. These findings suggest a role for SNX4 in synaptic vesicle recruitment at the active zone.

Original languageEnglish
Pages (from-to)1-17
Number of pages17
JournaleLife
Volume13
Early online date19 Dec 2024
DOIs
Publication statusPublished - 2024

Bibliographical note

Publisher Copyright:
© 2024, Poppinga et al.

Keywords

  • cell biology
  • hippocampal neuron
  • mouse
  • neuroscience
  • neurotranmission
  • plasticity
  • recycling endosome
  • vesicle recruitment

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