通过FK506结合蛋白稳定释放通道 (?? 氨酸受体) 功能
A B Brillantes1, K Ondrias, A Scott
1Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029.
Cell
|May 20, 1994
概括
结合FK506的蛋白质 (FKBP12) 对于氨酸受体 (RyR) 功能至关重要,它调节释放通道. 这项研究揭示了FKBP12的存在.
科学领域:
- 分子生物学分子生物学
- 细胞生理学 细胞生理学
- 生物化学 生物化学
背景情况:
- FKBP12是一种无处不在表达的林异构酶.
- 在这项研究之前,它的细胞功能在很大程度上是未知的.
- 已知FKBP12与氨酸受体 (RyR) 相互作用.
研究的目的:
- 阐明FKBP12.12的细胞功能.
- 确定FKBP12在RyR通道活性调节中的作用.
- 为了研究FKBP12对细胞内释放的影响.
主要方法:
- 在昆虫细胞中RyR和FKBP12的同时表达.
- 对RyR通道封锁特性进行分析.
- 使用FK506和拉帕米评估FKBP12异构酶活性.
主要成果:
- FKBP12显著增加了具有完全导电性的RyR通道的数量.
- 在咖啡因激活后,FKBP12降低了RyR通道的开放概率.
- FKBP12增加了RyR通道的平均开放时间.
- 抑制剂FK506和拉巴胺逆转了FKBP12对RyR通道的稳定作用.
结论:
- 这项研究确定了FKBP12的第一个自然细胞功能.
- FKBP12充当了氨酸受体通道关门的关键调节器.
- 功能性Ca2+释放通道复合体本质上包括FKBP12.
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