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

PLoS One. 2016 Jan 27;11(1):e0147379. doi: 10.1371/journal.pone.0147379. eCollection 2016.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Animals
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / metabolism*
  • Calcium / metabolism*
  • Calcium Channels, L-Type / genetics
  • Calcium Channels, L-Type / metabolism*
  • Exons
  • HEK293 Cells
  • Humans
  • Mice
  • RNA Splicing
  • Receptors, Antigen, T-Cell / metabolism*

Substances

  • CACNA1S protein, mouse
  • Calcium Channels, L-Type
  • Receptors, Antigen, T-Cell
  • Calcium