A1: Molecular basis of glycine- and GABAA receptor clustering and signaling - A2: Inhibitory synapses and synaptic plasticity: structural and functional coupling of local synthesis with inhibitory ion channels

A1：甘氨酸和 GABAA 受体聚类和信号传导的分子基础 - A2：抑制性突触和突触可塑性：局部合成与抑制性离子通道的结构和功能耦合

• 批准号: 5451430
• 负责人: Professor Dr. Joachim Kirsch
• 金额: --
• 依托单位: Institut für Anatomie und Zellbiologie
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2005
• 资助国家: 德国
• 起止时间: 2004-12-31 至 2007-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5451430?language=en
• 关键词: A1; Molecular; basis; glycine; GABAA

Many postsynaptic membrane specializations harboring glycine- (GlyR) or -amino butyric acid (GABA) receptors also contain scaffolds of the peripheral membrane protein gephyrin. Whereas the contribution of gephyrin, which interacts with the GlyR  subunit, to the formation and maintenance of glycinergic synapses has been amply documented, the functional role of other GlyR associated proteins is still unclear. We have identified a set of proteins interacting with GlyR 2 subunits, which are possibly involved in regulating protein synthesis and/or actin dynamics. We would like to continue our research on the functional characterization of these GlyR interacting proteins using biochemical and molecular biological approaches. The contribution of the newly identified components of inhibitory synapses shall be analysed both on the morphological and functional level. It is conceivable that dynamic changes in the composition of the protein machinery underneath inhibitory synapses may contribute to activity-dependent plastic changes and functional adaptations of synapses. Moreover, these subsynaptic proteins could be involved in the formation and maintenance of inhibitory synapses, the regulation of their developmental changes or modifications and secondary signaling cascades.

许多含有甘氨酸-（GlyR）或γ-氨基丁酸（GABA）受体的突触后膜特化也含有外周膜蛋白桥蛋白的支架。尽管与GlyR β亚基相互作用的桥蛋白对甘氨酸能突触的形成和维持的贡献已被充分证明，但其他GlyR相关蛋白的功能作用仍不清楚。我们已经确定了一组与GlyR β 2亚基相互作用的蛋白质，这可能涉及调节蛋白质合成和/或肌动蛋白动力学。我们想继续我们的研究，这些GlyR相互作用的蛋白质的功能特性，使用生物化学和分子生物学的方法。应在形态和功能水平上分析新鉴定的抑制性突触组分的贡献。可以想象的是，抑制性突触下的蛋白质机器组成的动态变化可能有助于突触的活性依赖性可塑性变化和功能适应。此外，这些突触下蛋白可能参与抑制性突触的形成和维持，调节其发育变化或修饰以及次级信号级联。