Abstract
Recent advances in imaging technology have highlighted that scaffold proteins and receptors are arranged in sub-synaptic nanodomains. The synaptic MAGUK scaffold protein MPP2 is a component of AMPA receptor-associated protein complexes and also binds to the synaptic cell adhesion molecule SynCAM1. Using super-resolution imaging, we now show that MPP2 and SynCAM1 are situated at the periphery of the postsynaptic density. In order to explore MPP2-associated protein complexes, we used a quantitative comparative mass spectrometry approach and identified multiple GABAA receptor subunits among the novel synaptic MPP2 interactors. We further show that GABAA receptors are found together with MPP2 in a subset of dendritic spines and thus highlight MPP2 as a scaffold molecule capable of acting as an adaptor molecule that links peripheral synaptic elements critical for inhibitory regulation to central structures at the PSD of glutamatergic synapses.
Footnotes
Abbreviations
AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; DIV, days in vitro; dSTORM, direct stochastic optical reconstruction microscopy; GABA, γ-aminobutyric acid; MAGUK, membrane-associated guanylate kinase; MPP2, membrane protein palmitoylated 2; NN, nearest neighbour; PSD, postsynaptic density; SIM, structured illumination microscopy