Parekh Anant B
Department of Physiology, Anatomy and Genetics, Parks Road Oxford OX1 3PT, UK.
Cell Calcium. 2017 May;63:20-23. doi: 10.1016/j.ceca.2016.12.003. Epub 2016 Dec 16.
CRAC channels are a major route for Ca influx in eukaryotic cells. The channels show prominent Ca-dependent inactivation through two spatially and temporally distinct mechanisms: fast inactivation, which develops over milliseconds and is triggered by Ca near the mouth of the channel and slow inactivation, which arises over tens of seconds and requires a rise in global cytosolic Ca. Slow inactivation is controlled physiologically by Ca uptake into mitochondria through the MCU. Site-directed mutagenesis studies on STIM1 and Orai1 have led to new molecular insight into how fast inactivation occurs. This review describes properties and molecular mechanisms that contribute to these important Ca-dependent inhibitory pathways.
CRAC通道是真核细胞中钙离子内流的主要途径。这些通道通过两种在空间和时间上不同的机制表现出显著的钙依赖性失活：快速失活，在数毫秒内发生，由通道口附近的钙离子触发；以及缓慢失活，在数十秒内出现，需要胞质溶胶中钙离子整体浓度升高。缓慢失活在生理上由通过MCU进入线粒体的钙摄取来控制。对STIM1和Orai1的定点诱变研究为快速失活的发生机制带来了新的分子见解。本综述描述了促成这些重要的钙依赖性抑制途径的特性和分子机制。
