Miniatura

Fitxers

253345.pdf (5.06 MB)

Tipus de document

Article

Versió

Versió publicada

Data de publicació

2022-08

Llicència de publicació

cc-by (c) Zeppillo, Tommaso et al., 2022
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/216575

Functional Neuroligin-2-MDGA1 interactions differentially regulate synaptic GABAARs and cytosolic gephyrin aggregation

Títol de la revista

Autors

Director/Tutor

ISSN de la revista

Títol del volum

Recurs relacionat

https://doi.org/10.1038/s42003-024-06789-z

Resum

Neuroligin-2 (Nlgn2) is a key synaptic adhesion protein at virtually all GABAergic synapses, which recruits GABAARs by promoting assembly of the postsynaptic gephyrin scaffold. Intriguingly, loss of Nlgn2 differentially affects subsets of GABAergic synapses, indicating that synapse-specific interactors and redundancies define its function, but the nature of these interactions remain poorly understood. Here we investigated how Nlgn2 function in hippocampal area CA1 is modulated by two proposed interaction partners, MDGA1 and MDGA2. We show that loss of MDGA1 expression, but not heterozygous deletion of MDGA2, ameliorates the abnormal cytosolic gephyrin aggregation, the reduction in inhibitory synaptic transmission and the exacerbated anxiety-related behaviour characterizing Nlgn2 knockout (KO) mice. Additionally, combined Nlgn2 and MDGA1 deletion causes an exacerbated layer-specific loss of gephyrin puncta. Given that both Nlgn2 and the MDGA1 have been correlated with many psychiatric disorders, our data support the notion that cytosolic gephyrin aggregation may represent an interesting target for novel therapeutic strategies.

Matèries

Ratolins (Animals de laboratori), Proteïnes portadores, Hipocamp (Cervell), Proteïnes de membrana

Matèries (anglès)

Mice (Laboratory animals), Carrier proteins, Hippocampus (Brain), Membrane proteins

Citació

Col·leccions

Articles publicats en revistes (Patologia i Terapèutica Experimental)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citació

SIGNORELLI, Janetti, ZEPPILLO, Tommaso, ALI, Heba, RAVICHANDRAN, Sowbarnika, RITTER, Tamara c., WENGER, Sally, LÓPEZ MURCIA, Francisco josé, GIDEONS, Erinn, SCHMEISSER, Michael j., WILTFANG, Jens, RHEE, Jeongseop, BROSE, Nils, TASCHENBERGER, Holger, KRUEGER-BURG, Dilja. Functional Neuroligin-2-MDGA1 interactions differentially regulate synaptic GABAARs and cytosolic gephyrin aggregation. _Communications Biology_. 2022. Vol. 7. [consulta: 27 de gener de 2026]. ISSN: 2399-3642. [Disponible a: https://hdl.handle.net/2445/216575]

Exportar metadades

JSON - METS

Compartir registre