In vivo nanoscopic landscape of neurexin ligands underlying anterograde synapse specification

Kazuya Nozawa, Taku Sogabe, Ayumi Hayashi, Junko Motohashi, Eriko Miura, Itaru Arai, Michisuke Yuzaki

Research output: Contribution to journalArticlepeer-review

Abstract

Excitatory synapses are formed and matured by the cooperative actions of synaptic organizers, such as neurexins (Nrxns), neuroligins (Nlgns), LRRTMs, and Cbln1. Recent super-resolution nanoscopy developments have revealed that many synaptic organizers, as well as glutamate receptors and glutamate release machinery, exist as nanoclusters within synapses. However, it is unclear how such nanodomains interact with each other to organize excitatory synapses in vivo. By applying X10 expansion microscopy to epitope tag knockin mice, we found that Cbln1, Nlgn1, and LRRTM1, which share Nrxn as a common presynaptic receptor, form overlapping or separate nanodomains depending on Nrxn with or without a sequence encoded by splice site 4. The size and position of glutamate receptor nanodomains of GluD1, NMDA, and AMPA receptors were regulated by Cbln1, Nlgn1, and LRRTM1 nanodomains, respectively. These findings indicate that Nrxns anterogradely regulate the postsynaptic nanoscopic architecture of glutamate receptors through competition and coordination of Nrxn ligands.

Original languageEnglish
JournalNeuron
DOIs
Publication statusPublished - 2022 Oct 5

Keywords

  • Cbln1
  • LRRTM1
  • expansion microscopy
  • nanocolumn
  • neurexin
  • neuroligin

ASJC Scopus subject areas

  • Neuroscience(all)

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