Numbers count: How STIM and Orai stoichiometry affect store-operated calcium entry

Cell Calcium
Michelle Yen, Richard S Lewis

Abstract

Substantial progress has been made in the past several years in establishing the stoichiometries of STIM and Orai proteins and understanding their influence on store-operated calcium entry. Depletion of ER Ca2+ triggers STIM1 to accumulate at ER-plasma membrane junctions where it binds and opens Ca2+ release-activated Ca2+ (CRAC) channels. STIM1 is a dimer, and release of Ca2+ from its two luminal domains is reported to promote their association as well as drive formation of higher-order STIM1 oligomers. The CRAC channel, originally thought to be tetrameric, is now considered to be a hexamer of Orai1 subunits based on crystallographic and electrophysiological studies. STIM1 binding activates CRAC channels in a highly nonlinear way, such that all six Orai1 binding sites must be occupied to account for the activation and signature properties of native channels. The structural basis of STIM1 engagement with the channel is currently unclear, with evidence suggesting that STIM1 dimers bind to individual or pairs of Orai1 subunits. This review examines evidence that has led to points of consensus and debate about STIM1 and Orai1 stoichiometries, and explains the importance of STIM-Orai complex stoichiometry for the regulation of stor...Continue Reading

Citations

Oct 2, 2019·Cold Spring Harbor Perspectives in Biology·Richard S Lewis
Apr 8, 2020·International Journal of Molecular Sciences·Sven KappelChristine Peinelt
May 25, 2020·Medical Microbiology and Immunology·Rebecca L GavinMichael G Tomlinson
May 9, 2019·Proceedings of the National Academy of Sciences of the United States of America·Fang YuKhaled Machaca
Jul 30, 2020·International Journal of Molecular Sciences·Elena ScreminCristina Fasolato
Dec 12, 2019·Journal of Cell Science·Dalia AlansaryNiels de Jonge
Jun 27, 2020·The Journal of General Physiology·Joseph L DynesMichael D Cahalan
Jan 8, 2021·Current Opinion in Physiology·Matthias SallingerIrene Frischauf
Dec 31, 2020·International Journal of Molecular Sciences·Dorina ZöphelAnnette Lis
Mar 3, 2021·Proceedings of the National Academy of Sciences of the United States of America·Yihan ShenColin W Taylor
Apr 3, 2021·Biochimica Et Biophysica Acta. Molecular Cell Research·Fernanda O LemosJan B Parys
Jun 3, 2021·Cells·Ayat S Hammad, Khaled Machaca
May 24, 2021·Cell Calcium·Raphael Courjaret, Khaled Machaca
Dec 9, 2021·The Journal of Physiology·Grigori Y RychkovGreg J Barritt

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