Scrimgeour N, Litjens T, Ma L, Barritt G J, Rychkov G Y
School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia 5005, Australia.
J Physiol. 2009 Jun 15;587(Pt 12):2903-18. doi: 10.1113/jphysiol.2009.170662. Epub 2009 Apr 29.
Two cellular proteins, stromal interaction molecule 1 (STIM1) and Orai1, are recently discovered essential components of the Ca2+ release activated Ca2+ (CRAC) channel. Orai1 polypeptides form the pore of the CRAC channel, while STIM1 plays the role of the endoplasmic reticulum Ca2+ sensor required for activation of CRAC current (I(CRAC)) by store depletion. It is not known, however, if the role of STIM1 is limited exclusively to Ca2+ sensing, or whether interaction between Orai1 and STIM1, either direct or indirect, also defines the properties of I(CRAC). In this study we investigated how the relative expression levels of ectopic Orai1 and STIM1 affect the properties of I(CRAC). The results show that cells expressing low Orai1 : STIM1 ratios produce I(CRAC) with strong fast Ca2+-dependent inactivation, while cells expressing high Orai1 : STIM1 ratios produce I(CRAC) with strong activation at negative potentials. Moreover, the expression ratio of Orai1 and STIM1 affects Ca2+, Ba2+ and Sr2+ conductance, but has no effect on the current in the absence of divalent cations. The results suggest that several key properties of Ca2+ channels formed by Orai1 depend on its interaction with STIM1, and that the stoichiometry of this interaction may vary depending on the relative expression levels of these proteins.
最近发现两种细胞蛋白，基质相互作用分子1（STIM1）和Orai1，是钙释放激活钙（CRAC）通道的必需组成部分。Orai1多肽形成CRAC通道的孔，而STIM1在内质网钙传感器中发挥作用，该传感器是通过储存耗竭激活CRAC电流（I(CRAC)）所必需的。然而，尚不清楚STIM1的作用是否仅限于钙传感，或者Orai1与STIM1之间的直接或间接相互作用是否也决定了I(CRAC)的特性。在本研究中，我们研究了异位Orai1和STIM1的相对表达水平如何影响I(CRAC)的特性。结果表明，表达低Orai1:STIM1比率的细胞产生具有强烈快速钙依赖性失活的I(CRAC)，而表达高Orai1:STIM1比率的细胞产生在负电位下具有强烈激活的I(CRAC)。此外，Orai1和STIM1的表达比率影响钙、钡和锶的电导，但对不存在二价阳离子时的电流没有影响。结果表明，由Orai1形成的钙通道的几个关键特性取决于其与STIM1的相互作用，并且这种相互作用的化学计量可能因这些蛋白质的相对表达水平而异。
