Evidence map›Paper›PMID 35254388›Full record

ArticleThe Journal of cell biology2022

Mechanosensitive calcium flashes promote sustained RhoA activation during tight junction remodeling.

Saranyaraajan Varadarajan, Shahana A Chumki, Rachel E Stephenson, Eileen R Misterovich, Jessica L Wu, Claire E Dudley, Ivan S Erofeev, Andrew B Goryachev, Ann L Miller

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of cell biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
6.0field-weighted citation impact, top 3% 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

47 citing papers in PubMed, 76 citations in OpenAlex.

  1. Tight junction structure, assembly and (dys)function.Nature reviews. Molecular cell biology · 2026
    Review
  2. Article
  3. Orai1 is required for CabioRxiv : the preprint server for biology · 2026
    Article
  4. Review
  5. Article
  6. Review
  7. Review
  8. Article
  9. A steady-state pool of calcium-dependent actin is maintained by Homer and controls epithelial mechanosensation.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Review
  15. Myosin 2 - A general contractor for the cytoskeleton.Current opinion in cell biology · 2025
    Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. 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

9 authors at 2 institutions in 2 countries.

Saranyaraajan VaradarajanDepartment of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI.ORCID 0000-0002-4473-9435
Shahana A ChumkiCellular and Molecular Biology Program, University of Michigan, Ann Arbor, MI.ORCID 0000-0002-5986-7093
Rachel E StephensonDepartment of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI.
Eileen R MisterovichDepartment of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI.
Jessica L WuDepartment of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI.
Claire E DudleyDepartment of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI.ORCID 0000-0003-0722-0068
Ivan S ErofeevCentre for Synthetic and Systems Biology, University of Edinburgh, Edinburgh, Scotland.
Andrew B GoryachevCentre for Synthetic and Systems Biology, University of Edinburgh, Edinburgh, Scotland.ORCID 0000-0002-1332-4819
Ann L MillerDepartment of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI.ORCID 0000-0002-7293-764X
University of Michigan · USUniversity of Edinburgh · GB

Funding

CELLULAR AND MOLECULAR BIOLOGY AT MICHIGANT32GM007315 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PUTHENVEEDU, MANOJKUMAR A · 1985 to 2021
$12.8M
Regulation of localized RhoA activity in dividing epithelial cellsR01GM112794 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MILLER, ANN LOUISE · 2015 to 2023
$3.0M
American Heart Association-American Stroke Association 20PRE35120588Biotechnology and Biological Sciences Research Council BB/P006507Biotechnology and Biological Sciences Research Council BB/P01190XNIGMS NIH HHS R01 GM112794NIGMS NIH HHS T32 GM007315NIH HHS 2R01 GM112794
6 · The paper itself

Abstract

Epithelial cell-cell junctions remodel in response to mechanical stimuli to maintain barrier function. Previously, we found that local leaks in tight junctions (TJs) are rapidly repaired by local, transient RhoA activation, termed "Rho flares," but how Rho flares are regulated is unknown. Here, we discovered that intracellular calcium flashes and junction elongation are early events in the Rho flare pathway. Both laser-induced and naturally occurring TJ breaks lead to local calcium flashes at the site of leaks. Additionally, junction elongation induced by optogenetics increases Rho flare frequency, suggesting that Rho flares are mechanically triggered. Depletion of intracellular calcium or inhibition of mechanosensitive calcium channels (MSCs) reduces the amplitude of calcium flashes and diminishes the sustained activation of Rho flares. MSC-dependent calcium influx is necessary to maintain global barrier function by regulating reinforcement of local TJ proteins via junction contraction. In all, we uncovered a novel role for MSC-dependent calcium flashes in TJ remodeling, allowing epithelial cells to repair local leaks induced by mechanical stimuli.

Indexed as

CalciumrhoA GTP-Binding ProteinTight JunctionsCalcium ChannelsEpithelial CellsSignal TransductionCalciumCalcium ChannelsrhoA GTP-Binding Protein

Identifiers

PMID35254388
PMCPMC8906493
OpenAlexW4220732250

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.