内源G蛋白结合受体的基因向光学控制
Prashant C Donthamsetti1, Johannes Broichhagen2, Vojtech Vyklicky1
1Department of Molecular and Cell Biology , University of California , Berkeley , California 94720 , United States.
Journal of the American Chemical Society
|July 11, 2019
概括
研究人员开发了一种新方法,maPORTL,使用光精确控制内源G蛋白合受体 (GPCR). 这一突破为研究生物系统中的GPCR功能提供了前所未有的时间和空间准确性.
科学领域:
- 神经科学
- 分子生物学
- 生物化学
背景情况:
- G蛋白结合受体 (GPCR) 是关键的膜蛋白,但对它们在生物系统中的功能进行精确控制仍然具有挑战性.
- 像DREADDs和optoXRs这样的现有工具使用工程蛋白质,其表达,局部化和与内源性合作伙伴的相互作用可能受到限制.
- 目前基于连接体的方法缺乏时间控制,限制了它们在动态生物学研究中的有用性.
研究的目的:
- 开发一种用于精确控制内源性GPCR的新方法.
- 调查内源性转基因谷氨酸受体2 (mGluR2) 在主皮质神经元中的功能.
- 为研究具有高空间时间分辨率的内源GPCR信号建立一个多功能平台.
主要方法:
- 使用化学,生物学和光的组合来控制内源mGluR2,一个C家族的GPCR.
- 开发了一种膜定可光切换的直角远程连接联体 (maPORTL) 系统.
- 使用可光切换的谷氨酸与基因向的血点进行受体激活.
主要成果:
- 在初级皮层神经元中实现内源mGluR2的快速,可逆和选择性激活.
- 证明光激活可以通过修改PORTL长度和膜属性来调整.
- 成功控制了具有细胞类型特异性和高时空精度的内源GPCR信号.
结论:
- maPORTL系统为精确控制内源GPCR提供了一个强大的新工具.
- 这种方法通过使用原生受体和光感应控制来克服现有方法的局限性.
- 这些发现为在各种生物环境中研究其他内源GPCR开发类似系统提供了一个模板.
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