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Publication : In vivo nanoscopic landscape of neurexin ligands underlying anterograde synapse specification.

First Author  Nozawa K Year  2022
Journal  Neuron Volume  110
Issue  19 Pages  3168-3185.e8
PubMed ID  36007521 Mgi Jnum  J:330884
Mgi Id  MGI:7355962 Doi  10.1016/j.neuron.2022.07.027
Citation  Nozawa K, et al. (2022) In vivo nanoscopic landscape of neurexin ligands underlying anterograde synapse specification. Neuron 110(19):3168-3185.e8
abstractText  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.
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