title: STIMulating stress fibers in endothelial cells.
abstract: The tight regulation of endothelial barrier function is of prime importance for physiology and, when this barrier is compromised, it contributes to pathophysiology. Endothelial cells that line the vasculature change shape, and monolayers of these cells react to thrombin with increased permeability. In vivo, this increased permeability allows for transudation of plasma proteins and edema formation. The endoplasmic reticulum-resident calcium (Ca2+) sensor stromal interacton molecule 1 (STIM1) is intimately involved in the cellular response to thrombin. In human endothelial cells, STIM1 fulfills its role within the thrombin signaling cascade independently of store-operated Ca2+ entry (SOCE) through Orai channels, and thus STIM1 emerges as a signaling component linking the thrombin receptor to RhoA activation and stress fiber formation. This SOCE-independent role of STIM1 highlights a surprising new aspect of this multifaceted cellular regulator.
authors.affiliation: Walther Straub Institute of Pharmacology and Toxicology, LMU Munich, Goethestrasse 33, D-80336 Munich, Germany. thomas.gudermann@lrz.uni-muenchen.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Gudermann
authors.forename: Dirk
authors.initials: D
authors.lastname: Steinritz
mesh_terms: D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000378:metabolism*; D000071740:ORAI1 Protein; D044463:Receptor, PAR-1 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D022502:Stress Fibers / Q000378:metabolism*; D000071737:Stromal Interaction Molecule 1; D013917:Thrombin / Q000494:pharmacology; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; D044463:Receptor, PAR-1; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; D013917:Thrombin; D020742:rhoA GTP-Binding Protein; D002118:Calcium