TY - JOUR
T1 - STIM1 controls endothelial barrier function independently of Orai1 and Ca2+ entry
AU - Shinde, Arti V.
AU - Motiani, Rajender K.
AU - Zhang, Xuexin
AU - Abdullaev, Iskandar F.
AU - Adam, Alejandro P.
AU - González-Cobos, José C.
AU - Zhang, Wei
AU - Matrougui, Khalid
AU - Vincent, Peter A.
AU - Trebak, Mohamed
PY - 2013/3/19
Y1 - 2013/3/19
N2 - 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.
AB - 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.
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U2 - 10.1126/scisignal.2003425
DO - 10.1126/scisignal.2003425
M3 - Article
C2 - 23512989
AN - SCOPUS:84875755342
SN - 1945-0877
VL - 6
SP - ra18
JO - Science signaling
JF - Science signaling
IS - 267
ER -