Sterol hindrance of Orai activation

STIM protein coupling in the activation of Orai channels.

STIM proteins are sensors of endoplasmic reticulum (ER) luminal Ca(2+) changes and rapidly translocate into near plasma membrane (PM) junctions to activate Ca(2+) entry through the Orai family of highly Ca(2+)-selective "store-operated" channels (SOCs). Dissecting the STIM-Orai coupling process is restricted by the abstruse nature of the ER-PM junctional domain. To overcome this problem, we stu...

Communication between N terminus and loop2 tunes Orai activation

Ca2+ release-activated Ca2+ (CRAC) channels constitute the major Ca2+ entry pathway into the cell. They are fully reconstituted via intermembrane coupling of the Ca2+-selective Orai channel and the Ca2+-sensing protein STIM1. In addition to the Orai C terminus, the main coupling site for STIM1, the Orai N terminus is indispensable for Orai channel gating. Although the extended transmembrane Ora...

CRACking the structure of Orai

Correspondence to: Andrew P. Braun Email: [email protected] Calcium (Ca) is well recognized as a key second messenger in a variety of eukaryotic signal transduction pathways, and nature has developed a number of regulatory mechanisms to mediate its cellular influx and efflux and its homeostasis within the cell. Stimulus-evoked release of Ca stored within internal organelles (i.e., endoplasmic ...

The many faces of Orai.

The STIM1/Orai signaling machinery

Ca(2+) influx via store-operated Ca(2+) release activated Ca(2+) (CRAC) channels represents a main signaling pathway for T-cell activation as well as mast-cell degranulation. The ER-located Ca(2+)-sensor, STIM1 and the Ca(2+)-selective ion pore, Orai1 in the membrane are sufficient to fully reconstitute CRAC currents. Their identification, but even more the recent structural resolution of both ...