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The STIM1: Orai Interaction.
Adv Exp Med Biol. 2016; 898:25-46.AE

Abstract

Ca(2+) influx via store-operated Ca(2+) release activated Ca(2+) (CRAC) channels represents a main signalling pathway for a variety of cell functions, including T-cell activation as well as mast-cell degranulation. Depletion of [Ca(2+)]ER results in activation of Ca(2+) channels within the plasmamembrane that mediate sustained Ca(2+) influx which is required for refilling Ca(2+) stores and down-stream Ca(2+) signalling. The CRAC channel is the best characterized store-operated channel (SOC) with well-defined electrophysiological properties. In recent years, the molecular components of the CRAC channel have been defined. 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. Stromal interaction molecule (STIM) 1 is localized in the ER, senses [Ca(2+)]ER and activates the CRAC channel upon store depletion by direct binding to Orai1 in the plasmamembrane. The identification of STIM1 and Orai1 and recently the structural resolution of both proteins by X-ray crystallography and nuclear magnetic resonance substantiated many findings from structure-function studies which has substantially improved the understanding of CRAC channel activation. Within this review, we summarize the functional and structural mechanisms of CRAC channel regulation, present a detailed overview of the STIM1/Orai1 signalling pathway where we focus on the critical domains mediating interactions and on the ion permeation pathway. We portray a mechanistic view of the steps in the dynamics of CRAC channel signalling ranging from STIM1 oligomerization over STIM1-Orai1 coupling to CRAC channel activation and permeation.

Authors+Show Affiliations

Institute of Biophysics, University of Linz, Linz, Austria. irene.frischauf@jku.at.Institute of Biophysics, University of Linz, Linz, Austria.Department of Physiology, University of Extremadura, Cáceres, Spain.Institute of Biophysics, University of Linz, Linz, Austria. christoph.romanin@jku.at.

Pub Type(s)

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

Language

eng

PubMed ID

27161223

Citation

Frischauf, Irene, et al. "The STIM1: Orai Interaction." Advances in Experimental Medicine and Biology, vol. 898, 2016, pp. 25-46.
Frischauf I, Fahrner M, Jardín I, et al. The STIM1: Orai Interaction. Adv Exp Med Biol. 2016;898:25-46.
Frischauf, I., Fahrner, M., Jardín, I., & Romanin, C. (2016). The STIM1: Orai Interaction. Advances in Experimental Medicine and Biology, 898, 25-46. https://doi.org/10.1007/978-3-319-26974-0_2
Frischauf I, et al. The STIM1: Orai Interaction. Adv Exp Med Biol. 2016;898:25-46. PubMed PMID: 27161223.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The STIM1: Orai Interaction. AU - Frischauf,Irene, AU - Fahrner,Marc, AU - Jardín,Isaac, AU - Romanin,Christoph, PY - 2016/5/11/entrez PY - 2016/5/11/pubmed PY - 2016/9/10/medline KW - CRAC channels KW - Orai1 KW - SOCE KW - STIM1 SP - 25 EP - 46 JF - Advances in experimental medicine and biology JO - Adv Exp Med Biol VL - 898 N2 - Ca(2+) influx via store-operated Ca(2+) release activated Ca(2+) (CRAC) channels represents a main signalling pathway for a variety of cell functions, including T-cell activation as well as mast-cell degranulation. Depletion of [Ca(2+)]ER results in activation of Ca(2+) channels within the plasmamembrane that mediate sustained Ca(2+) influx which is required for refilling Ca(2+) stores and down-stream Ca(2+) signalling. The CRAC channel is the best characterized store-operated channel (SOC) with well-defined electrophysiological properties. In recent years, the molecular components of the CRAC channel have been defined. 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. Stromal interaction molecule (STIM) 1 is localized in the ER, senses [Ca(2+)]ER and activates the CRAC channel upon store depletion by direct binding to Orai1 in the plasmamembrane. The identification of STIM1 and Orai1 and recently the structural resolution of both proteins by X-ray crystallography and nuclear magnetic resonance substantiated many findings from structure-function studies which has substantially improved the understanding of CRAC channel activation. Within this review, we summarize the functional and structural mechanisms of CRAC channel regulation, present a detailed overview of the STIM1/Orai1 signalling pathway where we focus on the critical domains mediating interactions and on the ion permeation pathway. We portray a mechanistic view of the steps in the dynamics of CRAC channel signalling ranging from STIM1 oligomerization over STIM1-Orai1 coupling to CRAC channel activation and permeation. SN - 0065-2598 UR - https://www.unboundmedicine.com/medline/citation/27161223/The_STIM1:_Orai_Interaction_ L2 - https://dx.doi.org/10.1007/978-3-319-26974-0_2 DB - PRIME DP - Unbound Medicine ER -