酶性维生素A2的产生使得红移光遗传学成为可能
Johanna Gerhards1, Leo I Volkov2, Joseph C Corbo2
1Institute of Physiology I, Medical Faculty, University of Bonn, 53125, Bonn, Germany.
Pflugers Archiv : European journal of physiology
|November 21, 2023
概括
这项研究引入了一种新的光遗传学策略,使用Cyp27c1酶产生维生素A2. 这提高了光门离子通道的红移光谱灵敏度,改善了组织透率,并减少了光学遗传学应用的光毒性.
科学领域:
- 视觉遗传学 视觉遗传学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 光遗传学使用光敏感蛋白来控制细胞,当前的执行器受到蓝色/绿色光敏感度的限制.
- 红光光遗传学提供了更好的组织透和减少光毒性,但需要红移的执行器.
- 由Cyp27c1产生的维生素A2会改变视觉色素的光谱敏感度.
研究的目的:
- 调查Cyp27c1生成的维生素A2是否可以将Channelrhodopsin-2 (ChR2) 和ReaChR的光谱灵敏度转移为红色.
- 探索Cyp27c1的共同表达作为实现红移光遗传学的方法.
主要方法:
- 使用了表达ChR2或ReaChR的HEK 293细胞.
- 补丁电生理学测量了不同波长的光电流.
- 高性能液体染色学 (HPLC) 证实了维生素A2的产生和Cyp27c1的局部化.
主要成果:
- 维生素A2化红移ChR2和ReaChR光谱灵敏度 (分别为6.8nm和12.4nm的λ50%).
- 在HEK 293细胞中Cyp27c1过度表达导致维生素A2的产生和线粒体局部化.
- Cyp27c1表达红移了ChR2和ReaChR λ50% (分别为10.5nm和14.3nm) 和增加了光电流.
结论:
- 共同表达Cyp27c1是一种可行的策略,以实现红移光遗传学.
- 这种方法提高了光遗传工具的光谱灵敏度,使其能够更深入地穿透组织.
- 通过Cyp27c1介导的维生素A2生产为红移光遗传学提供了一个有前途的体内方法.
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