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The synaptic scaffold protein MPP2 interacts with GABAA receptors at the periphery of the postsynaptic density of glutamatergic synapses.
- Source :
-
PLoS biology [PLoS Biol] 2022 Mar 21; Vol. 20 (3), pp. e3001503. Date of Electronic Publication: 2022 Mar 21 (Print Publication: 2022). - Publication 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.<br />Competing Interests: The authors have declared that no competing interests exist.
Details
- Language :
- English
- ISSN :
- 1545-7885
- Volume :
- 20
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- PLoS biology
- Publication Type :
- Academic Journal
- Accession number :
- 35312684
- Full Text :
- https://doi.org/10.1371/journal.pbio.3001503