T Cell Receptor Mediated Calcium Entry Requires Alternatively Spliced Cav1.1 Channels

细胞受体介导的钙离子进入需要选择性剪接的 Cav1.1 通道

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作者:Didi Matza, Abdallah Badou, Kathryn G Klemic, Judith Stein, Usha Govindarajulu, Monica J Nadler, Jean-Pierre Kinet, Amnon Peled, Oz M Shapira, Leonard K Kaczmarek, Richard A Flavell

Abstract

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.

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