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

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dc.contributor.authorTommaso Zeppillo
dc.contributor.authorHeba Ali
dc.contributor.authorSowbarnika Ravichandran
dc.contributor.authorTamara C. Ritter
dc.contributor.authorSally Wenger
dc.contributor.authorFrancisco J. López Murcia
dc.contributor.authorErinn Gideons
dc.contributor.authorJanetti Signorelli
dc.contributor.authorMichael J. Schmeisser
dc.contributor.authorJens Wiltfang
dc.contributor.authorJeongSeop Rhee
dc.contributor.authorNils Brose
dc.contributor.authorHolger Taschenberger
dc.contributor.authorDilja Krueger Burg
dc.date.accessioned2026-01-26T15:37:00Z
dc.date.available2026-01-26T15:37:00Z
dc.date.issued2024
dc.description.abstractNeuroligin-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.
dc.description.sponsorshipProjekt DEAL.
dc.identifier.doi10.1038/s42003-024-06789-z
dc.identifier.issn23993642
dc.identifier.urihttps://repositorioabierto.uantof.cl/handle/uantof/633
dc.language.isoen
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceCommunications Biology
dc.titleFunctional Neuroligin-2-MDGA1 interactions differentially regulate synaptic GABAARs and cytosolic gephyrin aggregation
dc.typeArticle
oaire.citation.volume7
organization.identifier.rorUniversidad de Antofagasta
uantof.identificator.departmentDepartamento Biomédico
uantof.identificator.facultyFacultad de Ciencias de la Salud
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