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The STIM1/Orai signaling machinery.
Channels (Austin). 2013 Sep-Oct; 7(5):330-43.C

Abstract

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 proteins by X-ray crystallography has substantially advanced the understanding of the activation mechanism of CRAC channels. In this review, we provide a detailed description of the STIM1/Orai1 signaling pathway thereby focusing on the critical domains mediating both, intra- as well as intermolecular interactions and on the ion permeation pathway. Based on the results of functional studies as well as the recently published crystal structures, we portray a mechanistic view of the steps in the CRAC channel signaling cascade ranging from STIM1 oligomerization over STIM1-Orai1 coupling to the ultimate Orai1 channel activation and permeation.

Authors+Show Affiliations

Institute of Biophysics; Johannes Kepler University Linz; Linz, Austria.Institute of Biophysics; Johannes Kepler University Linz; Linz, Austria.Institute of Biophysics; Johannes Kepler University Linz; Linz, Austria.Institute of Biophysics; Johannes Kepler University Linz; Linz, Austria.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

24107921

Citation

Fahrner, Marc, et al. "The STIM1/Orai Signaling Machinery." Channels (Austin, Tex.), vol. 7, no. 5, 2013, pp. 330-43.
Fahrner M, Derler I, Jardin I, et al. The STIM1/Orai signaling machinery. Channels (Austin). 2013;7(5):330-43.
Fahrner, M., Derler, I., Jardin, I., & Romanin, C. (2013). The STIM1/Orai signaling machinery. Channels (Austin, Tex.), 7(5), 330-43. https://doi.org/10.4161/chan.26742
Fahrner M, et al. The STIM1/Orai Signaling Machinery. Channels (Austin). 2013 Sep-Oct;7(5):330-43. PubMed PMID: 24107921.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The STIM1/Orai signaling machinery. AU - Fahrner,Marc, AU - Derler,Isabella, AU - Jardin,Isaac, AU - Romanin,Christoph, Y1 - 2013/10/09/ PY - 2013/10/11/entrez PY - 2013/10/11/pubmed PY - 2014/9/5/medline KW - CRAC channels KW - Orai KW - STIM KW - coiled-coil domain KW - immune system SP - 330 EP - 43 JF - Channels (Austin, Tex.) JO - Channels (Austin) VL - 7 IS - 5 N2 - 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 proteins by X-ray crystallography has substantially advanced the understanding of the activation mechanism of CRAC channels. In this review, we provide a detailed description of the STIM1/Orai1 signaling pathway thereby focusing on the critical domains mediating both, intra- as well as intermolecular interactions and on the ion permeation pathway. Based on the results of functional studies as well as the recently published crystal structures, we portray a mechanistic view of the steps in the CRAC channel signaling cascade ranging from STIM1 oligomerization over STIM1-Orai1 coupling to the ultimate Orai1 channel activation and permeation. SN - 1933-6969 UR - https://www.unboundmedicine.com/medline/citation/24107921/The_STIM1/Orai_signaling_machinery_ L2 - https://www.tandfonline.com/doi/full/10.4161/chan.26742 DB - PRIME DP - Unbound Medicine ER -