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The native ORAI channel trio underlies the diversity of Ca(2+) signaling events
The essential role of ORAI1 channels in receptor-evoked Ca(2+) signaling is well understood, yet little is known about the physiological activation of the ORAI channel trio natively expressed in all cells. The roles of ORAI2 and ORAI3 have remained obscure. We show that ORAI2 and ORAI3 channels play...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229178/ https://www.ncbi.nlm.nih.gov/pubmed/32415068 http://dx.doi.org/10.1038/s41467-020-16232-6 |
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author | Yoast, Ryan E. Emrich, Scott M. Zhang, Xuexin Xin, Ping Johnson, Martin T. Fike, Adam J. Walter, Vonn Hempel, Nadine Yule, David I. Sneyd, James Gill, Donald L. Trebak, Mohamed |
author_facet | Yoast, Ryan E. Emrich, Scott M. Zhang, Xuexin Xin, Ping Johnson, Martin T. Fike, Adam J. Walter, Vonn Hempel, Nadine Yule, David I. Sneyd, James Gill, Donald L. Trebak, Mohamed |
author_sort | Yoast, Ryan E. |
collection | PubMed |
description | The essential role of ORAI1 channels in receptor-evoked Ca(2+) signaling is well understood, yet little is known about the physiological activation of the ORAI channel trio natively expressed in all cells. The roles of ORAI2 and ORAI3 have remained obscure. We show that ORAI2 and ORAI3 channels play a critical role in mediating the regenerative Ca(2+) oscillations induced by physiological receptor activation, yet ORAI1 is dispensable in generation of oscillations. We reveal that ORAI2 and ORAI3 channels multimerize with ORAI1 to expand the range of sensitivity of receptor-activated Ca(2+) signals, reflecting their enhanced basal STIM1-binding and heightened Ca(2+)-dependent inactivation. This broadened bandwidth of Ca(2+) influx is translated by cells into differential activation of NFAT1 and NFAT4 isoforms. Our results uncover a long-sought role for ORAI2 and ORAI3, revealing an intricate control mechanism whereby heteromerization of ORAI channels mediates graded Ca(2+) signals that extend the agonist-sensitivity to fine-tune transcriptional control. |
format | Online Article Text |
id | pubmed-7229178 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-72291782020-06-05 The native ORAI channel trio underlies the diversity of Ca(2+) signaling events Yoast, Ryan E. Emrich, Scott M. Zhang, Xuexin Xin, Ping Johnson, Martin T. Fike, Adam J. Walter, Vonn Hempel, Nadine Yule, David I. Sneyd, James Gill, Donald L. Trebak, Mohamed Nat Commun Article The essential role of ORAI1 channels in receptor-evoked Ca(2+) signaling is well understood, yet little is known about the physiological activation of the ORAI channel trio natively expressed in all cells. The roles of ORAI2 and ORAI3 have remained obscure. We show that ORAI2 and ORAI3 channels play a critical role in mediating the regenerative Ca(2+) oscillations induced by physiological receptor activation, yet ORAI1 is dispensable in generation of oscillations. We reveal that ORAI2 and ORAI3 channels multimerize with ORAI1 to expand the range of sensitivity of receptor-activated Ca(2+) signals, reflecting their enhanced basal STIM1-binding and heightened Ca(2+)-dependent inactivation. This broadened bandwidth of Ca(2+) influx is translated by cells into differential activation of NFAT1 and NFAT4 isoforms. Our results uncover a long-sought role for ORAI2 and ORAI3, revealing an intricate control mechanism whereby heteromerization of ORAI channels mediates graded Ca(2+) signals that extend the agonist-sensitivity to fine-tune transcriptional control. Nature Publishing Group UK 2020-05-15 /pmc/articles/PMC7229178/ /pubmed/32415068 http://dx.doi.org/10.1038/s41467-020-16232-6 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Yoast, Ryan E. Emrich, Scott M. Zhang, Xuexin Xin, Ping Johnson, Martin T. Fike, Adam J. Walter, Vonn Hempel, Nadine Yule, David I. Sneyd, James Gill, Donald L. Trebak, Mohamed The native ORAI channel trio underlies the diversity of Ca(2+) signaling events |
title | The native ORAI channel trio underlies the diversity of Ca(2+) signaling events |
title_full | The native ORAI channel trio underlies the diversity of Ca(2+) signaling events |
title_fullStr | The native ORAI channel trio underlies the diversity of Ca(2+) signaling events |
title_full_unstemmed | The native ORAI channel trio underlies the diversity of Ca(2+) signaling events |
title_short | The native ORAI channel trio underlies the diversity of Ca(2+) signaling events |
title_sort | native orai channel trio underlies the diversity of ca(2+) signaling events |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229178/ https://www.ncbi.nlm.nih.gov/pubmed/32415068 http://dx.doi.org/10.1038/s41467-020-16232-6 |
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