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

ABSTRACT: Neuroligin-2 (Nlgn2) is a key synaptic adhesion protein at virtually all GABAergic synapses, which recruits GABA_ARs 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

SUBMITTER: Zeppillo T 

PROVIDER: S-EPMC11405390 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature