Development of genetically encoded fluorescent K+ probes

基因编码荧光 K 探针的开发

• 批准号: 394221884
• 负责人: Professor Dr. Nikolaus Plesnila
• 金额: --
• 依托单位: Institute of Lung Health and Immunity (LHI)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/394221884?language=en
• 关键词: Development; genetically; encoded; fluorescent; K+

Potassium ions (K+) accumulate within cells, the smallest units of life - a process, which is essential for the regulation of cellular key functions. K+ fluxes across the plasma membranes of excitable cells such as neurons, muscle- and gland cells are vital for their specific cell functions. Hence, an imbalance of the K+ homeostasis has profound implication at the cellular- and organismal level and is associated with a plethora of diseases including cardio-vascular-, neurological-, muscle-, and metabolic disorders as well as cancer. It is speculated that also within a cell K+ is unequally distributed among cellular compartments and respective intracellular K+ fluxes fundamentally contribute to cell functions and dysfunctions. Furthermore it is hypothesized that tiniest subcellular K+ signals have huge implications in cell physiology and pathology. However, our understanding in this regard is very limited due to the lack of suitable methods that allow monitoring K+ fluxes with high spatial and temporal resolution. This research project aims to develop novel fluorescent K+ biosensors that can be targeted to cellular organelles and subdomains of cells. Accordingly, the novel fluorescent probes will enable real-time recordings of local subcellular K+ signals and, thus, will allow investigating intracellular K+ fluxes to gain our understanding of the signaling role of this fundamental ion in health and diseases.

钾离子（K+）在细胞（最小的生命单位）内积累，这一过程对细胞关键功能的调节至关重要。可兴奋细胞（如神经元、肌肉细胞和腺体细胞）的质膜上的K+通量对其特定的细胞功能至关重要。因此，K+稳态失衡在细胞和机体水平上具有深远的影响，并与包括心血管、神经、肌肉、代谢紊乱以及癌症在内的大量疾病有关。据推测，在细胞内，K+在细胞间的分布也不均匀，细胞内K+的通量从根本上决定了细胞的功能和功能障碍。此外，我们假设最微小的亚细胞K+信号在细胞生理和病理中具有巨大的意义。然而，由于缺乏合适的方法来监测高时空分辨率的K+通量，我们在这方面的理解非常有限。本研究项目旨在开发新型荧光K+生物传感器，可靶向细胞器和细胞亚域。因此，新型荧光探针将能够实时记录局部亚细胞K+信号，因此，将允许研究细胞内K+通量，以获得我们对这一基本离子在健康和疾病中的信号作用的理解。