STIM1 Controls Endothelial Barrier Function Independently of Orai1 and Ca2+ Entry

Sci. Signal., 19 March 2013
Vol. 6, Issue 267, p. ra18
DOI: 10.1126/scisignal.2003425

STIM1 Controls Endothelial Barrier Function Independently of Orai1 and Ca2+ Entry

  1. Arti V. Shinde1,
  2. Rajender K. Motiani1,
  3. Xuexin Zhang1,2,
  4. Iskandar F. Abdullaev1,
  5. Alejandro P. Adam1,
  6. José C. González-Cobos1,2,
  7. Wei Zhang1,2,
  8. Khalid Matrougui3,*,
  9. Peter A. Vincent1, and
  10. Mohamed Trebak1,2,
  1. 1The Center for Cardiovascular Sciences, Albany Medical College, Albany, NY 12208, USA.
  2. 2Nanobioscience Constellation, College of Nanoscale Science and Engineering, University at Albany, State University of New York, Albany, NY 12203, USA.
  3. 3Department of Physiology, Hypertension and Renal Center of Excellence, Tulane University, New Orleans, LA 70112, USA.
  1. Corresponding author. E-mail: mtrebak{at}albany.edu
  • * Present address: Department of Physiology, Eastern Virginia School of Medicine, 700 West Olney Road, Norfolk, VA 23501, USA.

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, calcium-sensing 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.

Citation:

A. V. Shinde, R. K. Motiani, X. Zhang, I. F. Abdullaev, A. P. Adam, J. C. González-Cobos, W. Zhang, K. Matrougui, P. A. Vincent, and M. Trebak, STIM1 Controls Endothelial Barrier Function Independently of Orai1 and Ca2+ Entry. Sci. Signal. 6, ra18 (2013).

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