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
Share this article
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
  2. Download BibTeX
  3. Download .RIS

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.

Metrics

  • 1,979
    views
  • 346
    downloads
  • 9
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  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

Categories and tags

Research organism

Further reading

    1. Cell Biology

    Hypersensitive intercellular responses of endometrial stromal cells drive invasion in endometriosis

    Chun-Wei Chen, Jeffery B Chavez ... Bruce J Nicholson
    Research Article Updated

    Endometriosis is a debilitating disease affecting 190 million women worldwide and the greatest single contributor to infertility. The most broadly accepted etiology is that uterine endometrial cells retrogradely enter the peritoneum during menses, and implant and form invasive lesions in a process analogous to cancer metastasis. However, over 90% of women suffer retrograde menstruation, but only 10% develop endometriosis, and debate continues as to whether the underlying defect is endometrial or peritoneal. Processes implicated in invasion include: enhanced motility; adhesion to, and formation of gap junctions with, the target tissue. Endometrial stromal (ESCs) from 22 endometriosis patients at different disease stages show much greater invasiveness across mesothelial (or endothelial) monolayers than ESCs from 22 control subjects, which is further enhanced by the presence of EECs. This is due to the enhanced responsiveness of endometriosis ESCs to the mesothelium, which induces migration and gap junction coupling. ESC-PMC gap junction coupling is shown to be required for invasion, while coupling between PMCs enhances mesothelial barrier breakdown.

    1. Cell Biology

    Aging: Restoring bone healing potential

    Inês Sequeira
    Insight

    A combination of intermittent fasting and administering Wnt3a proteins to a bone injury can rejuvenate bone repair in aged mice.

    1. Cell Biology
    2. Genetics and Genomics

    Robust single-nucleus RNA sequencing reveals depot-specific cell population dynamics in adipose tissue remodeling during obesity

    Jisun So, Olivia Strobel ... Hyun Cheol Roh
    Tools and Resources

    Single-nucleus RNA sequencing (snRNA-seq), an alternative to single-cell RNA sequencing (scRNA-seq), encounters technical challenges in obtaining high-quality nuclei and RNA, persistently hindering its applications. Here, we present a robust technique for isolating nuclei across various tissue types, remarkably enhancing snRNA-seq data quality. Employing this approach, we comprehensively characterize the depot-dependent cellular dynamics of various cell types underlying mouse adipose tissue remodeling during obesity. By integrating bulk nuclear RNA-seq from adipocyte nuclei of different sizes, we identify distinct adipocyte subpopulations categorized by size and functionality. These subpopulations follow two divergent trajectories, adaptive and pathological, with their prevalence varying by depot. Specifically, we identify a key molecular feature of dysfunctional hypertrophic adipocytes, a global shutdown in gene expression, along with elevated stress and inflammatory responses. Furthermore, our differential gene expression analysis reveals distinct contributions of adipocyte subpopulations to the overall pathophysiology of adipose tissue. Our study establishes a robust snRNA-seq method, providing novel insights into the biological processes involved in adipose tissue remodeling during obesity, with broader applicability across diverse biological systems.