The postsynaptic MAGUK scaffold protein MPP2 organises a distinct interactome that incorporates GABAA receptors at the periphery of excitatory synapses

Schmerl, B.; Gimber, N.; Kuropka, B.; Rentsch, J.; Kunde, S.-A.; Ewers, H.; Freund, C.; Schmoranzer, J.; Rademacher, N.; Shoichet, S. A.

doi:10.1101/2020.05.29.123034

bioRxiv · 10.1101/2020.05.29.123034

The postsynaptic MAGUK scaffold protein MPP2 organises a distinct interactome that incorporates GABAA receptors at the periphery of excitatory synapses

Schmerl, B.·Gimber, N.·Kuropka, B.·Rentsch, J.·Kunde, S.-A.·Ewers, H.·Freund, C.·Schmoranzer, J.·Rademacher, N.·Shoichet, S. A.

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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.

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Schmerl, B., Gimber, N., Kuropka, B., Rentsch, J., Kunde, S.-A., Ewers, H., Freund, C., Schmoranzer, J., Rademacher, N., Shoichet, S. A.. 2020-06-01. The postsynaptic MAGUK scaffold protein MPP2 organises a distinct interactome that incorporates GABAA receptors at the periphery of excitatory synapses. https://doi.org/10.1101/2020.05.29.123034

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