A severe defect in CRAC Ca2+ channel activation and altered K+ channel gating in T cells from immunodeficient patients.
A severe defect in CRAC Ca2+ channel activation and altered K+ channel gating in T cells from immunodeficient patients.
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DOI：
10.1084/jem.20050687
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发表时间：
2005-09-05
期刊：
影响因子：
--
通讯作者：
Lewis RS
中科院分区：
文献类型：
--
作者：
Feske S;Prakriya M;Rao A;Lewis RS
TCR的参与通过Ca 2+释放激活的Ca 2+（CRAC）通道触发持续的Ca 2+进入，这有助于驱动T细胞对病原体应答的基因表达。CRAC通道在分子水平上的身份和激活机制是未知的。我们分析了来自SCID患者的T细胞中的离子通道表达和功能，其显示正常水平的1-2%的Ca 2+内流和严重受损的T细胞活化。Ca 2+内流的缺乏不是由于Ca 2+储存调节不足或参与控制淋巴细胞中Ca 2+内流的几个基因（kcna 3/Kv 1.3、kcnn 4/IKCa 1、trpc 1、trpc 3、trpv 6、stim 1）的表达。相反，电生理测量表明，流入缺陷是由于几乎完全缺乏功能性CRAC通道。CRAC通道活性的缺乏与电压敏感性降低和电压依赖性Kv1.3通道激活动力学减慢相关。这些结果表明，CRAC通道提供了人T细胞中由TCR激活的Ca 2+进入的主要（如果不是唯一的）途径。它们还为CRAC和Kv1.3通道之间的功能联系提供了证据，并为CRAC通道的分子遗传学研究建立了模型系统。
Engagement of the TCR triggers sustained Ca2+ entry through Ca2+ release-activated Ca2+ (CRAC) channels, which helps drive gene expression underlying the T cell response to pathogens. The identity and activation mechanism of CRAC channels at a molecular level are unknown. We have analyzed ion channel expression and function in T cells from SCID patients which display 1–2% of the normal level of Ca2+ influx and severely impaired T cell activation. The lack of Ca2+ influx is not due to deficient regulation of Ca2+ stores or expression of several genes implicated in controlling Ca2+ entry in lymphocytes (kcna3/Kv1.3, kcnn4/IKCa1, trpc1, trpc3, trpv6, stim1). Instead, electrophysiologic measurements show that the influx defect is due to a nearly complete absence of functional CRAC channels. The lack of CRAC channel activity is correlated with diminished voltage sensitivity and slowed activation kinetics of the voltage-dependent Kv1.3 channel. These results demonstrate that CRAC channels provide the major, if not sole, pathway for Ca2+ entry activated by the TCR in human T cells. They also offer evidence for a functional link between CRAC and Kv1.3 channels, and establish a model system for molecular genetic studies of the CRAC channel.
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DOI：
10.1084/jem.160.2.369
发表时间：
1984-08-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chandy KG;DeCoursey TE;Cahalan MD;McLaughlin C;Gupta S
通讯作者：
Gupta S
影响因子：
64.8
作者：
HOTH, M;PENNER, R
通讯作者：
PENNER, R
影响因子：
4.8
作者：
Beeton, C;Wulff, H;Chandy, KG
通讯作者：
Chandy, KG
影响因子：
4.8
作者：
Hanada, T;Lin, LH;Chishti, AH
通讯作者：
Chishti, AH
影响因子：
30.5
作者：
Bhakta, NR;Oh, DY;Lewis, RS
通讯作者：
Lewis, RS