LRRTM2 controls presynapse nano-organization and AMPA receptor sub-positioning through Neurexin-binding interface.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
11 Oct 2024
11 Oct 2024
Historique:
received:
08
08
2023
accepted:
30
09
2024
medline:
12
10
2024
pubmed:
12
10
2024
entrez:
11
10
2024
Statut:
epublish
Résumé
Synapses are organized into nanocolumns that control synaptic transmission efficacy through precise alignment of postsynaptic neurotransmitter receptors and presynaptic release sites. Recent evidence show that Leucine-Rich Repeat Transmembrane protein LRRTM2, highly enriched and confined at synapses, interacts with Neurexins through its C-terminal cap, but the role of this binding interface has not been explored in synapse formation and function. Here, we develop a conditional knock-out mouse model (cKO) to address the molecular mechanisms of LRRTM2 regulation, and its role in synapse organization and function. We show that LRRTM2 cKO specifically impairs excitatory synapse formation and function in mice. Surface expression, synaptic clustering, and membrane dynamics of LRRTM2 are tightly controlled by selective motifs in the C-terminal domain. Conversely, the N-terminal domain controls presynapse nano-organization and postsynapse AMPAR sub-positioning and stabilization through the recently identified Neurexin-binding interface. Thus, we identify LRRTM2 as a central organizer of pre- and post- excitatory synapse nanostructure through interaction with presynaptic Neurexins.
Identifiants
pubmed: 39394199
doi: 10.1038/s41467-024-53090-y
pii: 10.1038/s41467-024-53090-y
doi:
Substances chimiques
Receptors, AMPA
0
Nerve Tissue Proteins
0
Membrane Proteins
0
LRRTM2 protein, mouse
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
8807Subventions
Organisme : Agence Nationale de la Recherche (French National Research Agency)
ID : nanoPROBE, ANR-19-CE11-0025
Organisme : Agence Nationale de la Recherche (French National Research Agency)
ID : ANR-17-CE16-0028-01
Organisme : Fondation pour la Recherche Médicale (Foundation for Medical Research in France)
ID : DEQ20160334916
Informations de copyright
© 2024. The Author(s).
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