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Extracellular Vesicle Directed Exogenous Ion Channel Transport for Precise Manipulation of Biological Events
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2018-06-28 00:00:00 , DOI: 10.1021/acs.bioconjchem.8b00377
Linna Lyu 1 , Ming Hu 1 , Afu Fu 2 , Bengang Xing 1
Affiliation  

A larger number of human diseases are related to dysregulation or loss of cellular functions. Effective restoration of the missing or defective cellular functions is highly desirable for fundamental research and therapeutic applications. Inspired by the fantastic feature of cell-derived extracellular vesicles (EVs) that can transport various bioactive molecules between cells, herein, we developed a simple and efficient strategy based on EVs for transferring ion channels to recipient cells, thereby conferring specific biological function to the target cells and regulating the biological events. The constructed channel rhodopsin 2 (ChR2)-loaded EV (EV-ChR2) system can mediate the anchor of light-responsive ion channel ChR2 on the plasma membrane of recipient cells through membrane fusion. Upon blue light irradiation, the ion channel ChR2 was activated and opened, thus permitting the rapid flux of cation ions (e.g., calcium ion) across the plasma membrane of recipient cells. Moreover, the increased Ca2+ in the cytosol could effectively activate Ca2+-dependent transcription factors, further triggering the calcium signaling pathway. This strategy can be extended to modulate other cellular processes and provides a novel insight on the manipulation of biological events.

中文翻译:

胞外小泡定向外源离子通道运输的生物事件的精确操纵。

大量人类疾病与细胞功能失调或丧失有关。对于基础研究和治疗应用,非常需要有效地恢复缺失或有缺陷的细胞功能。受可在细胞之间转运各种生物活性分子的细胞源性细胞外囊泡(EV)奇妙功能的启发,我们在此基础上开发了一种基于EV的简单有效的策略,可将离子通道转移至受体细胞,从而赋予细胞特定的生物学功能。靶细胞并调节生物事件。构建的通道视紫红质2(ChR2)加载的EV(EV-ChR2)系统可以通过膜融合介导光响应离子通道ChR2在受体细胞质膜上的锚定。在蓝光照射下 离子通道ChR2被激活并打开,从而允许阳离子离子(例如钙离子)快速流过受体细胞的质膜。而且,钙的增加胞浆中的2+可以有效激活Ca 2+依赖性转录因子,从而进一步触发钙信号通路。此策略可以扩展以调节其他细胞过程,并提供有关生物学事件操纵的新见解。
更新日期:2018-06-28
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