Journal Article

DZNE-2022-00481

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The synaptic scaffold protein MPP2 interacts with GABAA receptors at the periphery of the postsynaptic density of glutamatergic synapses.

Schmerl, B. ; Gimber, N. ; Kuropka, B. ; Stumpf, A. ; Rentsch, J. ; Kunde, S.-A. ; von Sivers, J. ; Ewers, H. ; Schmitz, D.DZNE* ; Freund, C. ; Schmoranzer, J. ; Rademacher, N.DZNE* ; Shoichet, S. A.

2022
PLoS Lawrence, KS

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Please use a persistent id in citations: doi:10.1371/journal.pbio.3001503

Abstract: 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.

Keyword(s): Membrane Proteins: metabolism (MeSH) ; Post-Synaptic Density: metabolism (MeSH) ; Receptors, AMPA: metabolism (MeSH) ; Receptors, GABA-A (MeSH) ; Synapses: metabolism (MeSH) ; Membrane Proteins ; Receptors, AMPA ; Receptors, GABA-A

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Contributing Institute(s):

1. Network Dysfunction (AG Schmitz 1)
2. Synaptopathy (AG Garner)

Research Program(s):

1. 351 - Brain Function (POF4-351) (POF4-351)

Appears in the scientific report 2022

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