Matza Didi, Badou Abdallah, Klemic Kathryn G, Stein Judith, Govindarajulu Usha, Nadler Monica J, Kinet Jean-Pierre, Peled Amnon, Shapira Oz M, Kaczmarek Leonard K, Flavell Richard A
Department of Natural Sciences, The Open University of Israel, 1 University Road, Ra'anana, 4353701, Israel.
Genetic and Molecular Pathology Laboratory, Casablanca School of Medicine and Pharmacy, Hassan II University, Casablanca, Morocco.
PLoS One. 2016 Jan 27;11(1):e0147379. doi: 10.1371/journal.pone.0147379. eCollection 2016.
The process of calcium entry in T cells is a multichannel and multi-step process. We have studied the requirement for L-type calcium channels (Cav1.1) α1S subunits during calcium entry after TCR stimulation. High expression levels of Cav1.1 channels were detected in activated T cells. Sequencing and cloning of Cav1.1 channel cDNA from T cells revealed that a single splice variant is expressed. This variant lacks exon 29, which encodes the linker region adjacent to the voltage sensor, but contains five new N-terminal exons that substitute for exons 1 and 2, which are found in the Cav1.1 muscle counterpart. Overexpression studies using cloned T cell Cav1.1 in 293HEK cells (that lack TCR) suggest that the gating of these channels was altered. Knockdown of Cav1.1 channels in T cells abrogated calcium entry after TCR stimulation, suggesting that Cav1.1 channels are controlled by TCR signaling.
T细胞中钙离子内流的过程是一个多通道、多步骤的过程。我们研究了TCR刺激后钙离子内流过程中L型钙通道（Cav1.1）α1S亚基的需求。在活化的T细胞中检测到Cav1.1通道的高表达水平。从T细胞中对Cav1.1通道cDNA进行测序和克隆发现，表达的是单一剪接变体。该变体缺少编码与电压感受器相邻连接区的第29外显子，但包含五个新的N端外显子，可替代在Cav1.1肌肉对应物中发现的第1和第2外显子。在293HEK细胞（缺乏TCR）中使用克隆的T细胞Cav1.1进行的过表达研究表明，这些通道的门控发生了改变。T细胞中Cav1.1通道的敲低消除了TCR刺激后的钙离子内流，表明Cav1.1通道受TCR信号传导控制。
