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

The postsynaptic MAGUK scaffold protein MPP2 organises a distinct interactome that incorporates GABAA receptors at the periphery of excitatory synapses
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突触后 MAGUK 支架蛋白 MPP2 组织了一个独特的相互作用组,其中包含兴奋性突触周围的 GABAA 受体

DOI:
10.1101/2020.05.29.123034
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发表时间:
2020
期刊:
bioRxiv
影响因子:
--
通讯作者:
Shoichet
Shoichet
中科院分区:
--
文献类型:
--
作者:
Schmerl;Gimber;Kuropka;Rentsch;Freund;Schmoranzer;Rademacher;Shoichet

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成像技术的最新进展强调了支架蛋白和受体排列在突触亚纳米域中。突触 MAGUK 支架蛋白 MPP2 是 AMPA 受体相关蛋白复合物的组成部分,也与突触细胞粘附分子 SynCAM1 结合。使用超分辨率成像,我们现在表明 MPP2 和 SynCAM1 位于突触后密度的外围。为了探索 MPP2 相关蛋白复合物,我们使用定量比较质谱方法并在新型突触 MPP2 相互作用因子中鉴定了多个 GABAA 受体亚基。我们进一步表明,GABAA 受体与 MPP2 一起存在于树突棘的一个子集中,因此强调 MPP2 作为支架分子,能够充当接头分子,将抑制性调节至关重要的外周突触元件与谷氨酸能突触 PSD 的中心结构连接起来。
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 GABAAreceptor subunits among the novel synaptic MPP2 interactors. We further show that GABAAreceptors 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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