Signal Transduction

Understanding the STIM1-ulous

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Science  29 Mar 2013:
Vol. 339, Issue 6127, pp. 1497
DOI: 10.1126/science.339.6127.1497-b
CREDIT: ALEJANDRO P. ADAM, PETER A. VINCENT, AND MOHAMED TREBAK

The permeability of the circulatory system is carefully regulated, and disruption of the barrier can contribute to inflammation and sepsis. One important means of regulation is the action of thrombin on vascular endothelial cells. The receptor for thrombin initiates mobilization of calcium from intracellular stores, and Shinde et al. examined the role of such signaling in control of the endothelial barrier formed by human umbilical vein endothelial cells in culture. Signals that cause emptying of calcium stores lead to calcium entry across the plasma membrane by the Orai channel protein and its calcium sensor, stromal interacting molecule 1 (STIM1). STIM1 was required for increased permeability caused by thrombin; however, the role of STIM1 required neither calcium entry nor regulation of the Orai channel. Instead, STIM1 was required to activate the small guanosine triophosphatase RhoA, which coordinates remodeling of the actin cytoskeleton and reduces cell adhesion, which leads to increased permeability.

Sci. Signal. 6, ra18 (2013).

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