Mechanosensitive calcium flashes promote sustained RhoA activation during tight junction remodeling

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

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article numbere202105107
Number of pages28
JournalJournal of Cell Biology
Issue number4
Early online date7 Mar 2022
Publication statusPublished - 4 Apr 2022


  • calcium signaling
  • mechanotransduction
  • mechanosensitive calcium channel
  • active RhoA
  • Optogenetics
  • ZO-1
  • tight junctions
  • epithelial barrier function
  • Xenopus laevis
  • cell shape changes
  • junction elongation
  • junction contraction


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