Ultrafast membrane trafficking at synapses

突触的超快膜运输

• 批准号: 10899160
• 负责人: Shigeki Watanabe
• 金额: $ 10万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-15 至 2031-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10899160
• 关键词: Address; Behavioral; Defect; Electron Microscopy; Endocytosis; Event; Exocytosis; Lead; Mediating; Membrane; Membrane Lipids; Molecular; Neurons; Output; Play; Process; Proteins; Recording of previous events; Role; Signal Transduction; Speed; Stimulus; Synapses; Synaptic Vesicles; Synaptic plasticity; Techniques; Time; Visualization; experimental study; insight; millisecond; nervous system disorder; neurotransmission; novel strategies; response; tool; trafficking

Project Summary Neuronal signaling events at synapses determine circuit responses and result in specific behavioral outputs. This signaling is dynamic - modulated by the history of synaptic activity and perceived stimuli. Defects in neurotransmission also play a causative role in neurological disorders. However, our understanding of this process is limited by two factors: size and speed. Over the years, we have developed several techniques in electron microscopy to visualize changes in protein localization and synaptic ultrastructure associated with neuronal activity with millisecond temporal precision. Our experiments have revealed key insights into mechanisms of the synaptic vesicle cycle as well as new parameters controlling synaptic plasticity. However, many mysteries remain. How do exocytic and endocytic proteins coordinate to mediate membrane remodeling at synapses on a millisecond time scale? How do these proteins interact with each other and membrane lipids to perform their functions? How heterogenous are these processes? To address these questions, we will develop novel approaches in electron microscopy and leverage these tools to dissect the molecular mechanisms underlying synaptic vesicle exocytosis and endocytosis.

项目摘要 突触处的神经元信号事件决定电路响应并导致特定的行为输出。 这种信号是动态调制的历史突触活动和感知的刺激。缺陷 神经传递也在神经障碍中起致病作用。然而，我们对此的理解是， 这个过程受到两个因素的限制：大小和速度。多年来，我们开发了多种技术， 电子显微镜观察蛋白定位和突触超微结构的变化， 神经元活动的毫秒级时间精度。我们的实验揭示了 突触囊泡周期的机制以及控制突触可塑性的新参数。然而，在这方面， 许多谜团依然存在。胞吐和胞吞蛋白如何协调介导膜重塑 在毫秒的时间尺度上观察突触这些蛋白质如何相互作用和膜脂 来履行他们的职责这些过程的异质性有多大？为了解决这些问题，我们将 开发电子显微镜的新方法，并利用这些工具来解剖分子 突触囊泡胞吐和胞吞作用的机制。