The synaptic scaffold protein MPP2 interacts with GABA(A) 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.; Freund, C.; Schmoranzer, J.; Rademacher, N.; Shoichet, S.A.

The synaptic scaffold protein MPP2 interacts with GABA(A) receptors at the periphery of the postsynaptic density of glutamatergic synapses

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Item Type:	Article
Title:	The synaptic scaffold protein MPP2 interacts with GABA(A) receptors at the periphery of the postsynaptic density of glutamatergic synapses
Creators Name:	Schmerl, B., Gimber, N., Kuropka, B., Stumpf, A., Rentsch, J., Kunde, S.A., von Sivers, J., Ewers, H., Schmitz, D., Freund, C., Schmoranzer, J., Rademacher, N. and Shoichet, S.A.
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 GABA(A) receptors, manipulating MPP2 expression had effects on inhibitory synaptic transmission. 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.
Keywords:	Synapses, Neuronal Dendrites, Neurons, Hippocampus, Membrane Proteins, Protein Interactions, Protein Domains, Gamma-Aminobutyric Acid
Source:	PLoS Biology
ISSN:	1544-9173
Publisher:	Public Library of Science
Volume:	20
Number:	3
Page Range:	e3001503
Date:	21 March 2022
Official Publication:	https://doi.org/10.1371/journal.pbio.3001503
PubMed:	View item in PubMed

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