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.
Highlights
Calcium ion entry across the plasma membrane is necessary for the initiation of T lymphocyte activation and proliferation following antigen encounter [1,2,3,4,5]
We have previously observed in vivo that T cells from mice lacking β4 or AHNAK1 show reduced plasma membrane expression of Cav1.1 channels and reduced calcium entry after activation [13, 27, 30]
We show that, similar to their roles in other tissues, such as muscle, Cav1.1 channels are required for transmission of calcium into T cells after activation
Summary
Calcium ion entry across the plasma membrane is necessary for the initiation of T lymphocyte activation and proliferation following antigen encounter [1,2,3,4,5]. Activation of NFAT occurs upon elevation in cytosolic free calcium levels, which results in its retention in the nucleus and subsequent gene transcription [9, 10]. This process is modulated by variations in the amplitude and/or duration of the calcium signal [11], which subsequently affect gene transcription and T cell activation and differentiation
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