The Biomedical Research Centre, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
Immunity. 2011 Sep 23;35(3):349-60. doi: 10.1016/j.immuni.2011.07.011. Epub 2011 Aug 11.
The transport of calcium ions (Ca(2+)) to the cytosol is essential for immunoreceptor signaling, regulating lymphocyte differentiation, activation, and effector function. Increases in cytosolic-free Ca(2+) concentrations are thought to be mediated through two interconnected and complementary mechanisms: the release of endoplasmic reticulum Ca(2+) "stores" and "store-operated" Ca(2+) entry via plasma membrane channels. However, the identity of molecular components conducting Ca(2+) currents within developing and mature T cells is unclear. Here, we have demonstrated that the L-type "voltage-dependent" Ca(2+) channel Ca(V)1.4 plays a cell-intrinsic role in the function, development, and survival of naive T cells. Plasma membrane Ca(V)1.4 was found to be essential for modulation of intracellular Ca(2+) stores and T cell receptor (TCR)-induced rises in cytosolic-free Ca(2+), impacting activation of Ras-extracellular signal-regulated kinase (ERK) and nuclear factor of activated T cells (NFAT) pathways. Collectively, these studies revealed that Ca(V)1.4 functions in controlling naive T cell homeostasis and antigen-driven T cell immune responses.
钙离子（Ca(2+)）向细胞质的转运对于免疫受体信号转导至关重要，调节淋巴细胞的分化、激活和效应功能。细胞质游离 Ca(2+)浓度的增加被认为是通过两种相互关联和互补的机制介导的：内质网 Ca(2+)“储存”的释放和通过质膜通道的“储存操纵”Ca(2+)内流。然而，在发育中和成熟的 T 细胞中，介导 Ca(2+)电流的分子成分的身份尚不清楚。在这里，我们已经证明了 L 型“电压依赖性”Ca(2+)通道 Ca(V)1.4 在幼稚 T 细胞的功能、发育和存活中发挥细胞内固有作用。发现质膜 Ca(V)1.4 对于调节细胞内 Ca(2+)储存和 TCR 诱导的细胞质游离 Ca(2+)升高是必不可少的，这影响了 Ras-细胞外信号调节激酶（ERK）和激活的 T 细胞（NFAT）途径的核因子的激活。总的来说，这些研究表明 Ca(V)1.4 可控制幼稚 T 细胞的动态平衡和抗原驱动的 T 细胞免疫反应。
