engSchmerl, BettinaGimber, NiclasSchmoranzer, JanRademacher, NilsShoichet, Sarah AKuropka, BennoStumpf, AlexanderRentsch, JakobKunde, Stella-Amreivon Sivers, JudithEwers, HelgeSchmitz, DietmarFreund, ChristianThe synaptic scaffold protein MPP2 interacts with GABAA receptors at the periphery of the postsynaptic density of glutamatergic synapses.info:eu-repo/classification/ddc/610Membrane Proteins: metabolismPost-Synaptic Density: metabolismReceptors, AMPA: metabolismReceptors, GABA-ASynapses: metabolismMembrane ProteinsReceptors, AMPAReceptors, GABA-ARecent advances in imaging technology have highlighted that scaffold proteins and receptors are arranged in subsynaptic nanodomains. The synaptic membrane-associated guanylate kinase (MAGUK) scaffold protein membrane protein palmitoylated 2 (MPP2) is a component of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-associated protein complexes and also binds to the synaptic cell adhesion molecule SynCAM 1. Using superresolution imaging, we show that-like SynCAM 1-MPP2 is situated at the periphery of the postsynaptic density (PSD). In order to explore MPP2-associated protein complexes, we used a quantitative comparative proteomics approach and identified multiple γ-aminobutyric acid (GABA)A receptor subunits among novel synaptic MPP2 interactors. In line with a scaffold function for MPP2 in the assembly and/or modulation of intact GABAA receptors, manipulating MPP2 expression had effects on inhibitory synaptic transmission. We further show that GABAA receptors are found together with MPP2 in a subset of dendritic spines and thus highlight MPP2 as a scaffold that serves as an adaptor molecule, linking peripheral synaptic elements critical for inhibitory regulation to central structures at the PSD of glutamatergic synapses.PLoS biology 20(3), e3001503 (2022). doi:10.1371/journal.pbio.3001503info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionPLoS2022info:eu-repo/semantics/openAccessDEhttps://pub.dzne.de/record/163742https://pub.dzne.de/search?p=id:%22DZNE-2022-00481%22Researchersinfo:eu-repo/semantics/altIdentifier/pmid/pmid:35312684info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pbio.3001503info:eu-repo/semantics/altIdentifier/issn/1545-7885info:eu-repo/semantics/altIdentifier/issn/1544-9173