Evidence map›Paper›PMID 34705029›Full record

ArticleThe Journal of cell biology2021

Bidirectional regulation of calcium release-activated calcium (CRAC) channel by SARAF.

Elia Zomot, Hadas Achildiev Cohen, Inbal Dagan, Ruslana Militsin, Raz Palty

Open access · greenAbstract read
In one paragraph

Article in The Journal of cell biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.1field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 27 citations in OpenAlex.

  1. Article
  2. Article
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  5. CaAmerican journal of physiology. Cell physiology · 2025
    Article
  6. Article
  7. Split genetically encoded calcium indicators for interorganellar junctions.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
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  14. Article
  15. Store-operated CaPNAS nexus · 2023
    Article
  16. Article
  17. Review
  18. Review
  19. Review
  20. Photopharmacological modulation of native CRAC channels using azoboronate photoswitches.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Elia Zomot *Department of Biochemistry, Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.
Hadas Achildiev Cohen *Department of Biochemistry, Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.
Inbal DaganDepartment of Biochemistry, Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.
Ruslana MilitsinDepartment of Biochemistry, Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.
Raz PaltyDepartment of Biochemistry, Technion Integrated Cancer Center, Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.ORCID 0000-0001-6238-2399
Technion – Israel Institute of Technology · IL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Store-operated calcium entry (SOCE) through the Ca2+ release-activated Ca2+ (CRAC) channel is a central mechanism by which cells generate Ca2+ signals and mediate Ca2+-dependent gene expression. The molecular basis for CRAC channel regulation by the SOCE-associated regulatory factor (SARAF) remained insufficiently understood. Here we found that following ER Ca2+ depletion, SARAF facilitates a conformational change in the ER Ca2+ sensor STIM1 that relieves an activation constraint enforced by the STIM1 inactivation domain (ID; aa 475-483) and promotes initial activation of STIM1, its translocation to ER-plasma membrane junctions, and coupling to Orai1 channels. Following intracellular Ca2+ rise, cooperation between SARAF and the STIM1 ID controls CRAC channel slow Ca2+-dependent inactivation. We further show that in T lymphocytes, SARAF is required for proper T cell receptor evoked transcription. Taking all these data together, we uncover a dual regulatory role for SARAF during both activation and inactivation of CRAC channels and show that SARAF fine-tunes intracellular Ca2+ responses and downstream gene expression in cells.

Indexed as

CalciumCalcium Release Activated Calcium ChannelsHEK293 CellsHumansIntracellular Calcium-Sensing ProteinsIon Channel GatingJurkat CellsMembrane ProteinsNFATC Transcription FactorsORAI1 ProteinProtein BindingProtein ConformationStromal Interaction Molecule 1Stromal Interaction Molecule 2Transcription, GeneticCalciumCalcium Release Activated Calcium ChannelsIntracellular Calcium-Sensing ProteinsMembrane ProteinsNFATC Transcription FactorsORAI1 ProteinSARAF protein, humanStromal Interaction Molecule 1Stromal Interaction Molecule 2

Identifiers

PMID34705029
PMCPMC8562847
OpenAlexW3210066447

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.