1. Cell Biology
  2. Immunology and Inflammation

Intermittent Ca2+ signals mediated by Orai1 regulate basal T cell motility

  1. Tobias X Dong
  2. Shivashankar Othy
  3. Milton L Greenberg
  4. Amit Jairaman
  5. Chijioke Akunwafo
  6. Sabrina Leverrier
  7. Ying Yu
  8. Ian Parker
  9. Joseph L Dynes
  10. Michael D Cahalan  Is a corresponding author
  1. University of California, Irvine, United States
https://doi.org/10.7554/eLife.27827
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  1. Tobias X Dong
  2. Shivashankar Othy
  3. Milton L Greenberg
  4. Amit Jairaman
  5. Chijioke Akunwafo
  6. Sabrina Leverrier
  7. Ying Yu
  8. Ian Parker
  9. Joseph L Dynes
  10. Michael D Cahalan
(2017)
Intermittent Ca2+ signals mediated by Orai1 regulate basal T cell motility
eLife 6:e27827.
https://doi.org/10.7554/eLife.27827
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Abstract

Ca2+ influx through Orai1 channels is crucial for several T cell functions, but a role in regulating basal cellular motility has not been described. Here we show that inhibition of Orai1 channel activity increases average cell velocities by reducing the frequency of pauses in human T cells migrating through confined spaces, even in the absence of extrinsic cell contacts or antigen recognition. Utilizing a novel ratiometric genetically encoded cytosolic Ca2+ indicator, Salsa6f, which permits real-time monitoring of cytosolic Ca2+ along with cell motility, we show that spontaneous pauses during T cell motility in vitro and in vivo coincide with episodes of cytosolic Ca2+ signaling. Furthermore, lymph node T cells exhibited two types of spontaneous Ca2+ transients: short-duration 'sparkles' and longer duration global signals. Our results demonstrate that spontaneous and self-peptide MHC-dependent activation of Orai1 ensures random walk behavior in T cells to optimize immune surveillance.

Article and author information

Author details

  1. Tobias X Dong

    Department of Physiology and Biophysics, University of California, Irvine, Irvine, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5500-7099

  2. Shivashankar Othy

    Department of Physiology and Biophysics, University of California, Irvine, Irvine, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6832-5547

  3. Milton L Greenberg

    Department of Physiology and Biophysics, University of California, Irvine, Irvine, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Amit Jairaman

    Department of Physiology and Biophysics, University of California, Irvine, Irvine, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Chijioke Akunwafo

    Department of Physiology and Biophysics, University of California, Irvine, Irvine, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Sabrina Leverrier

    Department of Physiology and Biophysics, University of California, Irvine, Irvine, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Ying Yu

    Department of Physiology and Biophysics, University of California, Irvine, Irvine, United States
    Competing interests
    The authors declare that no competing interests exist.

  8. Ian Parker

    Department of Physiology and Biophysics, University of California, Irvine, Irvine, United States
    Competing interests
    The authors declare that no competing interests exist.

  9. Joseph L Dynes

    Department of Physiology and Biophysics, University of California, Irvine, Irvine, United States
    Competing interests
    The authors declare that no competing interests exist.

  10. Michael D Cahalan

    Department of Physiology and Biophysics, University of California, Irvine, Irvine, United States
    For correspondence
    mcahalan@uci.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4987-2526

Funding

National Institutes of Health (NS-14609)

  • Michael D Cahalan

National Science Foundation (IGERT DGE-1144901)

  • Tobias X Dong

National Institutes of Health (AI-121945)

  • Michael D Cahalan

National Institutes of Health (GM-41514)

  • Michael D Cahalan

National Institutes of Health (Training Grant T32-AI-060573)

  • Milton L Greenberg

National Institutes of Health (Training Grant T32-GM-008620)

  • Tobias X Dong

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Michael L Dustin, University of Oxford, United Kingdom

Ethics

Animal experimentation: All surgical procedures and animal maintenance complied with the National Institute of Health guidelines regarding the care and use of experimental animals and were approved by the Animal Care and Use Committee of University of California, Irvine (protocol 1998-1366).

Human subjects: All studies using human blood were approved by the University of California, Irvine Institutional Review Board (UCI IRB HS# 1995-460), and complied with all applicable UCI Research Policies for the conduct of human subjects research.

Version history

  1. Received: April 15, 2017
  2. Accepted: November 6, 2017
  3. Accepted Manuscript published: December 14, 2017 (version 1)
  4. Version of Record published: December 29, 2017 (version 2)

Copyright

© 2017, Dong et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Tobias X Dong
  2. Shivashankar Othy
  3. Milton L Greenberg
  4. Amit Jairaman
  5. Chijioke Akunwafo
  6. Sabrina Leverrier
  7. Ying Yu
  8. Ian Parker
  9. Joseph L Dynes
  10. Michael D Cahalan
(2017)
Intermittent Ca2+ signals mediated by Orai1 regulate basal T cell motility
eLife 6:e27827.
https://doi.org/10.7554/eLife.27827

Share this article

https://doi.org/10.7554/eLife.27827

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