%0 Journal Article
%A Schmerl, Bettina
%A Gimber, Niclas
%A Kuropka, Benno
%A Stumpf, Alexander
%A Rentsch, Jakob
%A Kunde, Stella-Amrei
%A von Sivers, Judith
%A Ewers, Helge
%A Schmitz, Dietmar
%A Freund, Christian
%A Schmoranzer, Jan
%A Rademacher, Nils
%A Shoichet, Sarah A
%T The synaptic scaffold protein MPP2 interacts with GABAA receptors at the periphery of the postsynaptic density of glutamatergic synapses.
%J PLoS biology
%V 20
%N 3
%@ 1544-9173
%C Lawrence, KS
%I PLoS
%M DZNE-2022-00481
%P e3001503
%D 2022
%X Recent 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.
%K Membrane Proteins: metabolism
%K Post-Synaptic Density: metabolism
%K Receptors, AMPA: metabolism
%K Receptors, GABA-A
%K Synapses: metabolism
%K Membrane Proteins (NLM Chemicals)
%K Receptors, AMPA (NLM Chemicals)
%K Receptors, GABA-A (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:35312684
%2 pmc:PMC8970474
%R 10.1371/journal.pbio.3001503
%U https://pub.dzne.de/record/163742