STIM1 controls endothelial barrier function independently of Orai1 and Ca2+ entry

Arti V. Shinde, Rajender K. Motiani, Xuexin Zhang, Iskandar F. Abdullaev, Alejandro P. Adam, José C. González-Cobos, Wei Zhang, Khalid Matrougui, Peter A. Vincent, Mohamed Trebak

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

Endothelial barrier function is critical for tissue fluid homeostasis, and its disruption contributes to various pathologies, including inflammation and sepsis. Thrombin is an endogenous agonist that impairs endothelial barrier function. We showed that the thrombin-induced decrease in transendothelial electric resistance of cultured human endothelial cells required the endoplasmic reticulum-localized, calciumsensing protein stromal interacting molecule 1 (STIM1), but was independent of Ca2+ entry across the plasma membrane and the Ca2+ release-activated Ca2+ channel protein Orai1, which is the target of STIM1 in the store-operated calcium entry pathway. We found that STIM1 coupled the thrombin receptor to activation of the guanosine triphosphatase RhoA, stimulation of myosin light chain phosphorylation, formation of actin stress fibers, and loss of cell-cell adhesion. Thus, STIM1 functions in pathways that are dependent on and independent of Ca2+ entry.

Original languageEnglish (US)
Pages (from-to)ra18
JournalScience Signaling
Volume6
Issue number267
DOIs
StatePublished - Mar 19 2013

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Shinde, A. V., Motiani, R. K., Zhang, X., Abdullaev, I. F., Adam, A. P., González-Cobos, J. C., Zhang, W., Matrougui, K., Vincent, P. A., & Trebak, M. (2013). STIM1 controls endothelial barrier function independently of Orai1 and Ca2+ entry. Science Signaling, 6(267), ra18. https://doi.org/10.1126/scisignal.2003425