Recent advances in imaging technology have highlighted that scaffold proteins and receptors are not distributed evenly throughout the postsynapse, but instead are arranged in subsynaptic nanodomains. Miniature inhibitory postsynaptic current MPP2,Īt postsynaptic sites on glutamatergic neurons, a complex arrangement of transmembrane receptors, scaffold molecules, and regulatory proteins enables the coordinated regulation of synaptic transmission (for reviews, see ). Membrane-associated guanylate kinase mIPSC, Liquid chromatography–mass spectrometry MAGUK, Α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid DIV,ĭirect stochastic optical reconstruction microscopy GABA, The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have declared that no competing interests exist. For fluorescence imaging we would like to acknowledge the assistance of the Core Facility AMBIO. For mass spectrometry, we would like to acknowledge the assistance of the Core Facility BioSupraMol, which is supported by the DFG. BS was additionally funded by a Charité PhD fellowship (‘Promotionsabschlussstipendium’). Further financial support was provided by the DFG-funded NeuroCure Cluster of Excellence (EXC 2049 grant recipient DS). All other relevant data are within the paper and its Supporting Information files."įunding: This work was primarily supported by grants from the ‘Deutsche Forschungsgemeinschaft’ (DFG), including project numbers 261102178 (grant recipient SAS) and 431572356 (grant recipients SAS and DS), and the DFG Collaborative Research Centers SFB 958 (grant recipients SAS, HE, CF, and JS) and TRR 186 (DFG project number 278001972 grant recipient HE). Custom Python scripts are available on GitHub: and. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ĭata Availability: Image analysis was performed with custom written FIJI/ImageJ scripts available at Github: and. Received: NovemAccepted: DecemPublished: March 21, 2022Ĭopyright: © 2022 Schmerl et al. Dalva, Thomas Jefferson University, UNITED STATES PLoS Biol 20(3):Īcademic Editor: Matthew B. (2022) The synaptic scaffold protein MPP2 interacts with GABA A receptors at the periphery of the postsynaptic density of glutamatergic synapses. We further show that GABA A 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.Ĭitation: Schmerl B, Gimber N, Kuropka B, Stumpf A, Rentsch J, Kunde S-A, et al. In line with a scaffold function for MPP2 in the assembly and/or modulation of intact GABA A receptors, manipulating MPP2 expression had effects on inhibitory synaptic transmission. 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. Using superresolution imaging, we show that-like SynCAM 1-MPP2 is situated at the periphery of the postsynaptic density (PSD). 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. Recent advances in imaging technology have highlighted that scaffold proteins and receptors are arranged in subsynaptic nanodomains.
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