Molecular analysis of assembly and function of surface AMPA-receptor complexes in the mammalian brain

哺乳动物大脑表面 AMPA 受体复合物的组装和功能的分子分析

• 批准号: 439189341
• 负责人: Professor Dr. Bernd Fakler
• 金额: --
• 依托单位: Lehrstuhl für Physiologie II - Molecular Physiology
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2020
• 资助国家: 德国
• 起止时间: 2019-12-31 至 2023-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/439189341?language=en
• 关键词: Molecular; analysis; assembly; function; surface

Glutamate receptors of the AMPA-type (AMPARs), the central players of excitatory neurotransmission in the brain, are multi-protein complexes whose molecular appearance and functional properties are encoded by their proteome (or interactome), the ensemble of their protein building blocks. These more than 30 distinct proteins identified by our original proteomic analyses define the biogenesis of the ‘receptor-core’ in the endoplasmic reticulum, as well as the assembly of the ‘receptor periphery’ finally building the mature AMPAR complexes at synaptic and extra-synaptic sites of the plasma membrane. In fact, our recent analyses strongly suggest that the constituents of the receptor periphery are major determinants for proper operation of AMPARs in synapses, as well as their activity-dependent dynamics and adaptations that are fundamental for learning and memory formation. This proposal aims at a comprehensive molecular understanding of the surface AMPAR complexes (characterized by the ‘periphery forming’ interactome constituents), with focus on their assembly, their dynamics, their interactions with synaptic proteins and their significance for receptor-mediated neurotransmission and plasticity. For this purposes we will apply an interdisciplinary approach comprising biochemistry and proteomic analyses, electro-physiology, as well as fluorescence- and electron-microscopy.

AMPA型（AMPARS）的谷氨酸受体和功能特性由其蛋白质组（或Interactome）编码，即它们的蛋白质构建块的集合Ticulum，以及“受体外围”的组装，最终在质膜的突触和突触部位上建立成熟的AMPAR复合物。适当地将AMPAR作为Theill作为提案。和蛋白质组学分析，以及Orescence-and Electron-Microscopicy。