Molecular mechanisms of AMPA receptor phosphorylation underlying synaptic plasticity

突触可塑性是学习和记忆的神经底物，在整个生命过程中都是必不可少的，它的下降阻碍了健康的衰老。AMPA型谷氨酸受体的功能和运输依赖于磷酸化的变化推动了突触的可塑性，但其分子机制尚不清楚。为了确定AMPA受体及其辅助蛋白胞内Ctail的磷酸化如何调节其结构和功能，我们将结合定量交联质谱学和膜片钳电生理学。这种跨学科方法的新组合将提供对关键蛋白质-蛋白质相互作用的洞察，这些相互作用是导致突触可塑性的基本过程。

Synaptic plasticity, the neural substrate of learning and memory, is essential throughout life and its decline impedes healthy aging. Phosphorylation-dependent changes in the function and trafficking of AMPA-type glutamate receptors drive synaptic plasticity, but the molecular mechanisms are poorly understood. To determine how phosphorylation of the intracellular Ctails of AMPA receptors and their auxiliary proteins modulates their structure and function we will combine quantitative cross-linking coupled to mass spectrometry and patch-clamp electrophysiology. This novel combination of interdisciplinary approaches will provide insight into the key protein-protein interactions that underlie a fundamental process responsible for synaptic plasticity.