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Immunological Disorders: Regulation of Ca2+ Signaling in T Lymphocytes

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Store-Operated Ca²⁺ Entry (SOCE) Pathways

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 993))

Abstract

Engagement of T cell receptors (TCRs) with cognate antigens triggers cascades of signaling pathways in helper T cells. TCR signaling is essential for the effector function of helper T cells including proliferation, differentiation, and cytokine production. It also modulates effector T cell fate by inducing cell death, anergy (nonresponsiveness), exhaustion, and generation of regulatory T cells. One of the main axes of TCR signaling is the Ca2+-calcineurin-nuclear factor of activated T cells (NFAT) signaling pathway. Stimulation of TCRs triggers depletion of intracellular Ca2+ store and, in turn, activates store-operated Ca2+ entry (SOCE) to raise the intracellular Ca2+ concentration. SOCE in T cells is mediated by the Ca2+ release-activated Ca2+ (CRAC) channels, which have been very well characterized in terms of their electrophysiological properties. Identification of STIM1 as a sensor to detect depletion of the endoplasmic reticulum (ER) Ca2+ store and Orai1 as the pore subunit of CRAC channels has dramatically advanced our understanding of the regulatory mechanism of Ca2+ signaling in T cells. In this review, we discuss our current understanding of Ca2+ signaling in T cells with specific focus on the mechanism of CRAC channel activation and regulation via protein interactions. In addition, we will discuss the role of CRAC channels in effector T cells, based on the analyses of genetically modified animal models.

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Acknowledgments

This work was supported by National Institute of Health grants AI-083432 and AI109059 (Y.G.).

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Authors and Affiliations

  1. Department of Physiology, David Geffen School of Medicine at UCLA, 53-266 CHS, 10833 Le Conte Avenue, Los Angeles, CA, 90095, USA

    Sonal Srikanth, Jin Seok Woo & Yousang Gwack

  2. Department of Molecular Immunology, Beckman Research Institute, City of Hope, Duarte, CA, USA

    Zuoming Sun

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  1. Sonal Srikanth
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  2. Jin Seok Woo
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  3. Zuoming Sun
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  4. Yousang Gwack
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Correspondence to Yousang Gwack .

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  1. Institute of Biophysics, Medical University of Graz, Graz, Austria

    Klaus Groschner

  2. Institute of Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria

    Wolfgang F. Graier

  3. Institute of Biophysics, Johannes Kepler University Linz, Linz, Austria

    Christoph Romanin

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Srikanth, S., Woo, J.S., Sun, Z., Gwack, Y. (2017). Immunological Disorders: Regulation of Ca2+ Signaling in T Lymphocytes. In: Groschner, K., Graier, W., Romanin, C. (eds) Store-Operated Ca²⁺ Entry (SOCE) Pathways. Advances in Experimental Medicine and Biology, vol 993. Springer, Cham. https://doi.org/10.1007/978-3-319-57732-6_21

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