title: STIM1 controls endothelial barrier function independently of Orai1 and Ca2+ entry.
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.
authors.affiliation: The Center for Cardiovascular Sciences, Albany Medical College, Albany, NY 12208, USA.
authors.forename: Arti V
authors.initials: AV
authors.lastname: Shinde
authors.forename: Rajender K
authors.initials: RK
authors.lastname: Motiani
authors.forename: Xuexin
authors.initials: X
authors.lastname: Zhang
authors.forename: Iskandar F
authors.initials: IF
authors.lastname: Abdullaev
authors.forename: Alejandro P
authors.initials: AP
authors.lastname: Adam
authors.forename: José C
authors.initials: JC
authors.lastname: González-Cobos
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Khalid
authors.initials: K
authors.lastname: Matrougui
authors.forename: Peter A
authors.initials: PA
authors.lastname: Vincent
authors.forename: Mohamed
authors.initials: M
authors.lastname: Trebak
mesh_terms: D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D002478:Cells, Cultured; D017097:Electric Impedance; D004721:Endoplasmic Reticulum / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D005455:Fluorescent Antibody Technique; D057809:HEK293 Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D018994:Myosin Light Chains / Q000378:metabolism; D009219:Myosin-Light-Chain Kinase / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D000071740:ORAI1 Protein; D010766:Phosphorylation; D034622:RNA Interference; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D000071737:Stromal Interaction Molecule 1; D050052:TRPC Cation Channels / Q000235:genetics / Q000378:metabolism; D000074287:TRPC6 Cation Channel; D013917:Thrombin / Q000494:pharmacology; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D008565:Membrane Proteins; D018994:Myosin Light Chains; D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; D050052:TRPC Cation Channels; C489571:TRPC4 ion channel; D000074287:TRPC6 Cation Channel; C117032:TRPC6 protein, human; C096351:transient receptor potential cation channel, subfamily C, member 1; D009219:Myosin-Light-Chain Kinase; D013917:Thrombin; D020742:rhoA GTP-Binding Protein; D002118:Calcium