通过两孔通道,NAADP从酸性有机体中调动
Peter J Calcraft1, Margarida Ruas, Zui Pan
1Centre for Integrative Physiology, College of Medicine and Veterinary Medicine, University of Edinburgh, Hugh Robson Building, Edinburgh EH8 9XD, Scotland, UK.
Nature
|April 24, 2009
概括
两孔通道 (TPC) 被确定为尼古丁酸腺因二核酸 (NAADP) 受体. 这些TPC从酸性器官中释放,影响更广泛的细胞信号通路.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生理学 生理学 生理学
背景情况:
- 从细胞内储存中的 (Ca2+) 调动对于细胞信号传递至关重要.
- 伊诺西托-1,4,5-三酸盐 (InsP3) 和循环ADP核糖通过InsP3Rs和RyRs调节Ca2+的释放.
- 对于NAADP的点和受体仍有争议,尽管与溶酶体相关的部分也存在影响.
研究的目的:
- 为了确定NAADP受体的分子特征.
- 阐明TPC在NAADP介导的Ca2+信号传递中的作用.
- 了解TPCs对细胞Ca2+调节的贡献.
主要方法:
- 人类TPC1,TPC2和TPC3在HEK293细胞中的表达.
- 评估NAADP与TPC2丰富膜的结合亲和力.
- 在各种条件下研究NAADP诱导的Ca2+释放,包括溶酶体质子梯度破坏和TPC2切除.
主要成果:
- TPCs (TPC1,TPC2,TPC3) 局部存在于内体和溶体膜上.
- TPC2表现出高亲和度NAADP结合,并调解NAADP诱导的Ca2+从溶酶体相关储存中的释放.
- 由NAADP诱导的Ca2+释放取决于溶酶体质子梯度和TPC2表达,并且可以通过InsP3Rs放大Ca2+信号.
结论:
- TPCs作为NAADP受体起作用,从酸性有机体中释放Ca2+.
- 这种Ca2+的释放可以启动通过质细胞/内质细胞网膜的二次信号事件.
- TPC为细胞Ca2+信号的调节和组织以及NAADP的生理作用提供了新的见解.
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