TY  - JOUR
AU  - Schmerl, Bettina
AU  - Gimber, Niclas
AU  - Kuropka, Benno
AU  - Stumpf, Alexander
AU  - Rentsch, Jakob
AU  - Kunde, Stella-Amrei
AU  - von Sivers, Judith
AU  - Ewers, Helge
AU  - Schmitz, Dietmar
AU  - Freund, Christian
AU  - Schmoranzer, Jan
AU  - Rademacher, Nils
AU  - Shoichet, Sarah A
TI  - The synaptic scaffold protein MPP2 interacts with GABAA receptors at the periphery of the postsynaptic density of glutamatergic synapses.
JO  - PLoS biology
VL  - 20
IS  - 3
SN  - 1544-9173
CY  - Lawrence, KS
PB  - PLoS
M1  - DZNE-2022-00481
SP  - e3001503
PY  - 2022
AB  - 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.
KW  - Membrane Proteins: metabolism
KW  - Post-Synaptic Density: metabolism
KW  - Receptors, AMPA: metabolism
KW  - Receptors, GABA-A
KW  - Synapses: metabolism
KW  - Membrane Proteins (NLM Chemicals)
KW  - Receptors, AMPA (NLM Chemicals)
KW  - Receptors, GABA-A (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:35312684
C2  - pmc:PMC8970474
DO  - DOI:10.1371/journal.pbio.3001503
UR  - https://pub.dzne.de/record/163742
ER  -