Molecular mechanisms of AMPA receptor phosphorylation underlying synaptic plasticity

AMPA受体磷酸化导致突触可塑性的分子机制

• 批准号: 2091942
• 金额: --
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2091942
• 关键词: Molecular; mechanisms; AMPA; receptor; phosphorylation

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.

突触可塑性是学习和记忆的神经基质，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的磷酸化依赖性变化驱动突触可塑性，但分子机制知之甚少。为了确定AMPA受体及其辅助蛋白的细胞内Ctail的磷酸化如何调节它们的结构和功能，我们将联合收割机定量交联与质谱和膜片钳电生理学结合。这种跨学科方法的新组合将提供对关键蛋白质-蛋白质相互作用的深入了解，这些相互作用是负责突触可塑性的基本过程的基础。