Badou Abdallah, Basavappa Srisaila, Desai Rooma, Peng You-Qing, Matza Didi, Mehal Wajahat Z, Kaczmarek Leonard K, Boulpaep Emile L, Flavell Richard A
Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA.
Science. 2005 Jan 7;307(5706):117-21. doi: 10.1126/science.1100582.
Calcium is known to play vital roles in diverse physiological processes, and it is known that voltage-gated calcium channels (Cav) mediate calcium influx in excitable cells. However, no consensus exists on the molecular identity of the calcium channels present in nonexcitable cells such as T lymphocytes. Here, we demonstrate that T lymphocytes express both regulatory beta4 and poreforming Cav1 alpha1 subunits of Cav channels. Cav beta4-mutant T lymphocytes fail to acquire normal functions and display impairment in the calcium response, activation of the transcription factor NFAT, and cytokine production. Although Cav1 channels of lymphocytes retain their voltage dependency, T cell receptor stimulation dramatically increases channel opening, providing a new mechanism for calcium entry in lymphocytes.
众所周知，钙在多种生理过程中发挥着至关重要的作用，并且已知电压门控钙通道（Cav）介导可兴奋细胞中的钙内流。然而，对于非可兴奋细胞（如T淋巴细胞）中存在的钙通道的分子身份尚无共识。在此，我们证明T淋巴细胞表达Cav通道的调节性β4和形成孔道的Cav1 α1亚基。Cav β4突变的T淋巴细胞无法获得正常功能，并在钙反应、转录因子NFAT的激活和细胞因子产生方面表现出损伤。尽管淋巴细胞的Cav1通道保持其电压依赖性，但T细胞受体刺激会显著增加通道开放，为淋巴细胞中的钙内流提供了一种新机制。
