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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. and Gimber, N. and Kuropka, B. and Stumpf, A. and Rentsch, J. and Kunde, S.A. and von Sivers, J. and Ewers, H. and Schmitz, D. and Freund, C. and Schmoranzer, J. and 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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