Ultrafast membrane trafficking at synapses

突触的超快膜运输

• 批准号: 10663455
• 负责人: Shigeki Watanabe
• 金额: $ 89.63万
• 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/10663455
• 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确定电路响应并导致特定的行为输出。 该信号传导是动态的 - 由突触活动和感知刺激的历史调节。缺陷 神经传递在神经系统疾病中也起因作用。但是，我们对此的理解 过程受两个因素的限制：尺寸和速度。多年以来，我们已经开发了几种技术 电子显微镜以可视化蛋白质定位的变化和突触超微结构 神经元活性，具有毫秒的时间精度。我们的实验揭示了关键的见解 突触囊泡周期的机制以及控制突触可塑性的新参数。然而， 仍然存在许多谜团。外生细胞和内吞蛋白如何坐标以介导膜重塑 在毫秒时尺度上的突触？这些蛋白质如何相互作用和膜脂质 执行其功能？这些过程的异质性如何？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剖析分子 突触囊泡胞吐和内吞作用的机制。