1. Cell Biology
  2. Neuroscience

Regulation of store-operated Ca2+ entry by IP3 receptors independent of their ability to release Ca2+

  1. Pragnya Chakraborty
  2. Bipan Kumar Deb
  3. Vikas Arige
  4. Thasneem Musthafa
  5. Sundeep Malik
  6. David I Yule
  7. Colin W Taylor  Is a corresponding author
  8. Gaiti Hasan  Is a corresponding author
  1. National Centre for Biological Sciences, India
  2. University of California, Berkeley, United States
  3. University of Rochester, United States
  4. University of Cambridge, United Kingdom
https://doi.org/10.7554/eLife.80447
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Cite this article
  1. Pragnya Chakraborty
  2. Bipan Kumar Deb
  3. Vikas Arige
  4. Thasneem Musthafa
  5. Sundeep Malik
  6. David I Yule
  7. Colin W Taylor
  8. Gaiti Hasan
(2023)
Regulation of store-operated Ca2+ entry by IP3 receptors independent of their ability to release Ca2+
eLife 12:e80447.
https://doi.org/10.7554/eLife.80447
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Abstract

Loss of endoplasmic reticular (ER) Ca2+ activates store-operated Ca2+ entry (SOCE) by causing the ER localized Ca2+ sensor STIM to unfurl domains that activate Orai channels in the plasma membrane at membrane contact sites (MCS). Here we demonstrate a novel mechanism by which the inositol 1,4,5 trisphosphate receptor (IP3R), an ER-localized IP3-gated Ca2+ channel, regulates neuronal SOCE. In human neurons, SOCE evoked by pharmacological depletion of ER-Ca2+ is attenuated by loss of IP3Rs, and restored by expression of IP3Rs even when they cannot release Ca2+, but only if the IP3Rs can bind IP3. Imaging studies demonstrate that IP3Rs enhance association of STIM1 with Orai1 in neuronal cells with empty stores; this requires an IP3-binding site, but not a pore. Convergent regulation by IP3Rs, may tune neuronal SOCE to respond selectively to receptors that generate IP3.

Data availability

The data supporting the findings of this study are available within the manuscript. All other data supporting the findings of this study are available in source data file of respective figures.

Article and author information

Author details

  1. Pragnya Chakraborty

    Tata Institute of Fundamental Research, National Centre for Biological Sciences, Bangalore, India
    Competing interests
    No competing interests declared.

  2. Bipan Kumar Deb

    Department of Molecular and Cell Biology, University of California, Berkeley, California, United States
    Competing interests
    No competing interests declared.

  3. Vikas Arige

    Department of Pharmacology and Physiology, University of Rochester, Rochester, United States
    Competing interests
    No competing interests declared.

  4. Thasneem Musthafa

    Tata Institute of Fundamental Research, National Centre for Biological Sciences, Bangalore, India
    Competing interests
    No competing interests declared.

  5. Sundeep Malik

    Department of Pharmacology and Physiology, University of Rochester, Rochester, United States
    Competing interests
    No competing interests declared.

  6. David I Yule

    Department of Pharmacology and Physiology, University of Rochester, Rochester, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6743-0668

  7. Colin W Taylor

    Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom
    For correspondence
    cwt1000@cam.ac.uk
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7771-1044

  8. Gaiti Hasan

    Tata Institute of Fundamental Research, National Centre for Biological Sciences, Bangalore, India
    For correspondence
    gaiti@ncbs.res.in
    Competing interests
    Gaiti Hasan, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7194-383X

Funding

Department of Science and Technology, Ministry of Science and Technology, India (DST/INSPIRE Fellowship/2017/IF170360)

  • Pragnya Chakraborty

Department of Biotechnology, Ministry of Science and Technology, India (BT/PR6371/COE/34/19/2013)

  • Gaiti Hasan

Tata Institute of Fundamental Research (NCBS,TIFR core support)

  • Gaiti Hasan

Wellcome Trust (101844)

  • Colin W Taylor

Biotechnology and Biological Sciences Research Council (BB/T012986/1)

  • Colin W Taylor

NIH (DE014756)

  • David I Yule

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

Copyright

© 2023, Chakraborty 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. Pragnya Chakraborty
  2. Bipan Kumar Deb
  3. Vikas Arige
  4. Thasneem Musthafa
  5. Sundeep Malik
  6. David I Yule
  7. Colin W Taylor
  8. Gaiti Hasan
(2023)
Regulation of store-operated Ca2+ entry by IP3 receptors independent of their ability to release Ca2+
eLife 12:e80447.
https://doi.org/10.7554/eLife.80447

Share this article

https://doi.org/10.7554/eLife.80447

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