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@ARTICLE{Schmerl:163742,
author = {Schmerl, Bettina and Gimber, Niclas and Kuropka, Benno and
Stumpf, Alexander and Rentsch, Jakob and Kunde, Stella-Amrei
and von Sivers, Judith and Ewers, Helge and Schmitz, Dietmar
and Freund, Christian and Schmoranzer, Jan and Rademacher,
Nils and Shoichet, Sarah A},
title = {{T}he synaptic scaffold protein {MPP}2 interacts with
{GABAA} receptors at the periphery of the postsynaptic
density of glutamatergic synapses.},
journal = {PLoS biology},
volume = {20},
number = {3},
issn = {1544-9173},
address = {Lawrence, KS},
publisher = {PLoS},
reportid = {DZNE-2022-00481},
pages = {e3001503},
year = {2022},
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.},
keywords = {Membrane Proteins: metabolism / Post-Synaptic Density:
metabolism / Receptors, AMPA: metabolism / Receptors, GABA-A
/ Synapses: metabolism / Membrane Proteins (NLM Chemicals) /
Receptors, AMPA (NLM Chemicals) / Receptors, GABA-A (NLM
Chemicals)},
cin = {AG Schmitz 1 / AG Garner},
ddc = {610},
cid = {I:(DE-2719)1810004 / I:(DE-2719)1810001},
pnm = {351 - Brain Function (POF4-351)},
pid = {G:(DE-HGF)POF4-351},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:35312684},
pmc = {pmc:PMC8970474},
doi = {10.1371/journal.pbio.3001503},
url = {https://pub.dzne.de/record/163742},
}