Calcium microdomains at the immunological synapse: how ORAI channels, mitochondria and calcium pumps generate local calcium signals for efficient T-cell activation
Calcium microdomains at the immunological synapse: how ORAI channels, mitochondria and calcium pumps generate local calcium signals for efficient T-cell activation
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DOI：
10.1038/emboj.2011.289
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发表时间：
2011-10-05
期刊：
影响因子：
11.4
通讯作者：
Hoth, Markus
中科院分区：
文献类型：
--
作者：
Quintana, Ariel;Pasche, Mathias;Hoth, Markus
细胞极化使得能够将信号传导限制在微域中。淋巴细胞在形成成熟的免疫突触（IS）后的极化对于钙依赖性T细胞活化是必不可少的。在这里，我们分析钙微区在IS与全内反射荧光显微镜。我们发现，在IS形成后，质膜下钙信号足够低，以防止奥赖通道的钙依赖性失活。这是通过将线粒体定位在奥赖通道附近来实现的。此外，我们发现质膜钙ATP酶（PMCAs）重新分布到线粒体下方的区域，这阻止了PMCA上调，并减少了局部的钙输出。这种纳米级分布-仅在IS形成后诱导-使通过奥赖通道的钙内流效率最大化，同时降低PMCA的钙清除率，导致更持续的NFAT活性和随后的T细胞活化。The EMBO Journal（2011）30，3895-3912. doi：10.1038/doj.2011.289; 2011年8月16日在线发布
Cell polarization enables restriction of signalling into microdomains. Polarization of lymphocytes following formation of a mature immunological synapse (IS) is essential for calcium-dependent T-cell activation. Here, we analyse calcium microdomains at the IS with total internal reflection fluorescence microscopy. We find that the subplasmalemmal calcium signal following IS formation is sufficiently low to prevent calcium-dependent inactivation of ORAI channels. This is achieved by localizing mitochondria close to ORAI channels. Furthermore, we find that plasma membrane calcium ATPases (PMCAs) are re-distributed into areas beneath mitochondria, which prevented PMCA up-modulation and decreased calcium export locally. This nano-scale distribution-only induced following IS formation-maximizes the efficiency of calcium influx through ORAI channels while it decreases calcium clearance by PMCA, resulting in a more sustained NFAT activity and subsequent activation of T cells. The EMBO Journal (2011) 30, 3895-3912. doi:10.1038/emboj.2011.289; Published online 16 August 2011