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 PMID:21835646  

The Ca(v)1.4 calcium channel is a critical regulator of T cell receptor signaling and naive T cell homeostasis.

Kyla Omilusik | John J Priatel | Xiaoxi Chen | Yiwen Teresa Wang | Hongjian Xu | Kyung Bok Choi | Rayshad Gopaul | Adam McIntyre-Smith | Hung-Sia Teh | Rusung Tan | N Torben Bech-Hansen | Douglas Waterfield | David Fedida | Simon V Hunt | Wilfred A Jefferies
Immunity | 2011

The transport of calcium ions (Ca(2+)) to the cytosol is essential for immunoreceptor signaling, regulating lymphocyte differentiation, activation, and effector function. Increases in cytosolic-free Ca(2+) concentrations are thought to be mediated through two interconnected and complementary mechanisms: the release of endoplasmic reticulum Ca(2+) "stores" and "store-operated" Ca(2+) entry via plasma membrane channels. However, the identity of molecular components conducting Ca(2+) currents within developing and mature T cells is unclear. Here, we have demonstrated that the L-type "voltage-dependent" Ca(2+) channel Ca(V)1.4 plays a cell-intrinsic role in the function, development, and survival of naive T cells. Plasma membrane Ca(V)1.4 was found to be essential for modulation of intracellular Ca(2+) stores and T cell receptor (TCR)-induced rises in cytosolic-free Ca(2+), impacting activation of Ras-extracellular signal-regulated kinase (ERK) and nuclear factor of activated T cells (NFAT) pathways. Collectively, these studies revealed that Ca(V)1.4 functions in controlling naive T cell homeostasis and antigen-driven T cell immune responses.

Pubmed ID: 21835646

Research resources used in this publication

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Antibodies used in this publication

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Associated grants

  • Agency: Canadian Institutes of Health Research, Canada
    Id: MOP-102698

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