Structure, Regulation and Biophysics of ICRAC, STIM/Orai1

  • Isabella Derler
  • Josef Madl
  • Gerhard Schütz
  • Christoph Romanin
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 740)


Ca2+ release activated Ca2+ (CRAC) channels mediate robust Ca2+ influx when the endoplasmic reticulum Ca2+ stores are depleted. This essential process for T-cell activation as well as degranulation of mast cells involves the Ca2+ sensor STIM1, located in the endoplasmic reticulum and the Ca2+ selective Orai1 channel in the plasma membrane. Our review describes the CRAC signaling pathway, the activation of which is initiated by a drop in the endoplasmic Ca2+ level sensed by STIM1. This in term induces multimerisation and puncta-formation of STIM1 proteins is followed by their coupling to and activation of Orai channels. Consequently Ca2+ entry is triggered through the Orai pore into the cytosol with subsequent closure of the channel by Ca2+-dependent inactivation. We will portray a mechanistic view of the events coupling STIM1 to Orai activation based on their structure and biophysics.


(STIM1) stromal interaction molecule 1 (CRAC) Ca2+ release-actived Ca2+ current (SOC) store-operated current (CMD) CRAC modulatory domain (SCID) severe combined immune deficiency (HEK) human embryonal kidney (ARC) arachidonate regulated Ca2+ (SHD) STIM1 homomerization domain (CAD) CRAC activating domain (SOAR) STIM1 Orai activating region FRET Förster Resonance Energy Transfer (ROS) reactive oxygen species (TM) transmembrane (2-APB) 2-aminoethoxydiphenyl borate 



Isabella Derler (T466) is a Hertha-Firnberg scholarship holder. This work was supported by the Austrian Science Foundation (FWF): project P22565 to C.R., Ph.D. Program W1201 “Molecular Bioanalytics” and project Y250-B3 to G.J.S.


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Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  1. 1.Institute of BiophysicsUniversity of LinzLinzAustria
  2. 2.Institute of Applied PhysicsVienna University of TechnologyViennaAustria

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