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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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