Nanometer-scale molecular organization of neurotransmitter and hormone release sites characterized by immuno electron microscopy

通过免疫电子显微镜表征的神经递质和激素释放位点的纳米级分子组织

• 批准号: 381877226
• 负责人: Professor Dr. Manfred W. Kilimann
• 金额: --
• 依托单位: Abteilung Molekulare Neurobiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2023-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/381877226?language=en
• 关键词: Nanometer; scale; molecular; organization; neurotransmitter

The interior of living cells is subtly compartmentalized and structured. In this way, counterproductive interactions are avoided and productive interactions become more efficent, precise and fast. Nerve cells, because of their elaborate cell architecture and the speed and precision of their synaptic signaling, demand a particularly high degree of molecular order. Electron microscopy allows to determine cellular structures with spatial resolution down to the size of protein molecules. It therefore lends itself to the determination of supramolecular arrangements on the nanometer scale, thus bridging the gap between the molecular and the cellular dimension.What is the spatial arrangement of proteins involved in the synaptic exocytosis of neurotransmitter vesicles? I imagine that they are precisely juxtaposed, like the cogwheels of a machine, to ensure the very fast, precise and finely controlled signal transmission at synapses. Previous immuno-electron microscopic work by my laboratory has determined the "in-situ topology" of Aczonin/Piccolo and some of its interaction partners at conventional synapses of the cerebellum. These studies are now to be extended to a specialized synapse type (ribbon synapses) and to endocrine cells, with more refined techniques. The results will lead to a better understanding how the molecular and supramolecular organization of the exocytosis machinery contributes to the specific functional properties of these synapse and cell types.

活细胞的内部被巧妙地划分和结构化。通过这种方式，避免了适得其反的互动，并使有效的互动变得更加有效，准确和快速。神经细胞，由于其复杂的细胞结构和突触信号的速度和精确性，需要特别高的分子秩序。电子显微镜可以确定细胞结构的空间分辨率下降到蛋白质分子的大小。因此，它有助于确定纳米尺度上的超分子排列，从而弥合分子和细胞维度之间的差距。神经递质囊泡突触胞吐作用中涉及的蛋白质的空间排列是什么？我想象它们精确地并列在一起，就像机器的齿轮一样，以确保突触上非常快速，精确和精细控制的信号传输。我的实验室以前的免疫电镜工作已经确定了Aczonin/Piccolo和它的一些相互作用的合作伙伴在传统的小脑突触的“原位拓扑结构”。这些研究现在将扩展到一个专门的突触类型（带状突触）和内分泌细胞，更精细的技术。结果将导致更好地理解胞吐机制的分子和超分子组织如何有助于这些突触和细胞类型的特定功能特性。