LRRC8蛋白形成体积调节的离子通道,感知离子强度
Ruhma Syeda1, Zhaozhu Qiu2, Adrienne E Dubin1
1Department of Molecular and Cellular Neuroscience, Howard Hughes Medical Institute, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
Cell
|January 30, 2016
概括
由LRRC8蛋白形成的体积调节离子通道 (VRAC) 孔. 低质压通过降低细胞质离子强度来激活VRAC,揭示了道
科学领域:
- 细胞生物学
- 离子通道生理学
- 细胞体积调节的分子机制
背景情况:
- 在透应激过程中,体积调节的离子通道 (VRAC) 维持细胞体积.
- 已知SWELL1 (LRRC8A) 是一个重要的VRAC成分.
- VRAC的孔形成子单元和封闭机制在很大程度上是未知的.
研究的目的:
- 为了识别VRAC的孔形成子单位.
- 通过细胞胀阐明VRAC的封闭机制.
主要方法:
- 将LRRC8复合物的生物化学复合成二层脂质.
- 复制道的电生理记录.
- 在不同的透条件和离子强度下分析通道活动.
主要成果:
- LRRC8子单元 (SWELL1等) 组合成异构的VRAC复合体 (约800kDa).
- 复制后的LRRC8复合物形成由度梯度激活的功能性离子通道.
- 道导电性取决于LRRC8子单位的组成.
- 低细胞质离子强度会独立于透梯度激活LRRC8复合体.
结论:
- LRRC8蛋白形成了体积调节的离子通道的孔隙.
- 通过低压力激活VRAC是通过细胞质离子强度的下降进行的.
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