Feedback modulation of Orai1α and Orai1β protein content mediated by STIM proteins

Store-operated Ca2+ entry is a mechanism controlled by the filling state of the intracellular Ca2+ stores, predominantly the endoplasmic reticulum (ER), where ER-resident proteins STIM1 and STIM2 orchestrate the activation of Orai channels in the plasma membrane, and Orai1 playing a predominant role...

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Autores: Nieto-Felipe, Joel, Macías-Diaz, Álvaro, Jiménez-Velarde, Vanesa, López, José J., Salido, Gines M., Smani, Tarik, Jardín, Isaac, Rosado, Juan A.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/390850
Acceso en línea:http://hdl.handle.net/10261/390850
https://api.elsevier.com/content/abstract/scopus_id/85205541665
Access Level:acceso abierto
Palabra clave:Orai1α
Orai1β
STIM1
STIM2
Store‐operated Ca2+ entry
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spelling Feedback modulation of Orai1α and Orai1β protein content mediated by STIM proteinsNieto-Felipe, JoelMacías-Diaz, ÁlvaroJiménez-Velarde, VanesaLópez, José J.Salido, Gines M.Smani, TarikJardín, IsaacRosado, Juan A.Orai1αOrai1βSTIM1STIM2Store‐operated Ca2+ entryStore-operated Ca2+ entry is a mechanism controlled by the filling state of the intracellular Ca2+ stores, predominantly the endoplasmic reticulum (ER), where ER-resident proteins STIM1 and STIM2 orchestrate the activation of Orai channels in the plasma membrane, and Orai1 playing a predominant role. Two forms of Orai1, Orai1α and Orai1β, have been identified, which arises the question whether they are equally regulated by STIM proteins. We demonstrate that STIM1 preferentially activates Orai1α over STIM2, yet both STIM proteins similarly activate Orai1β. Under resting conditions, there is a pronounced association between STIM2 and Orai1α. STIM1 and STIM2 are also shown to influence the protein levels of the Orai1 variants, independently of Ca2+ influx, via lysosomal degradation. Interestingly, Orai1α and Orai1β appear to selectively regulate the protein level of STIM1, but not STIM2. These observations offer crucial insights into the regulatory dynamics between STIM proteins and Orai1 variants, enhancing our understanding of the intricate processes that fine-tune intracellular Ca2+ signaling.We thank Sandra Alvarado for assistance in some experiments and María Barriga for technical assistance. This research is part of the projects PID2022-136279NB-C21 and PID2022-136279NB-C22 funded by MICIU/AEI/10.13039/501100011033/ and by “ERDF A way of making Europe”, and Junta de Extremadura-Fondo Europeo de Desarrollo Regional (FEDER; Grant IB20007 and GR18061) to JAR and TS. JN-F and AM are supported by a contract from AEI/Spanish Ministry of Science and Innovation and INVESTIGO, respectively.Peer reviewedJohn Wiley & SonsNieto-Felipe, Joel [0000-0001-6342-3893]Smani, Tarik [0000-0002-1877-7438]Jardín, Isaac [0000-0003-4575-8264]Rosado, Juan A. [0000-0002-9749-2325]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252025info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/390850https://api.elsevier.com/content/abstract/scopus_id/85205541665reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)InglésThe underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.1002/jcp.31450https://doi.org/10.1002/jcp.31450Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3908502026-05-22T06:33:51Z
dc.title.none.fl_str_mv Feedback modulation of Orai1α and Orai1β protein content mediated by STIM proteins
title Feedback modulation of Orai1α and Orai1β protein content mediated by STIM proteins
spellingShingle Feedback modulation of Orai1α and Orai1β protein content mediated by STIM proteins
Nieto-Felipe, Joel
Orai1α
Orai1β
STIM1
STIM2
Store‐operated Ca2+ entry
title_short Feedback modulation of Orai1α and Orai1β protein content mediated by STIM proteins
title_full Feedback modulation of Orai1α and Orai1β protein content mediated by STIM proteins
title_fullStr Feedback modulation of Orai1α and Orai1β protein content mediated by STIM proteins
title_full_unstemmed Feedback modulation of Orai1α and Orai1β protein content mediated by STIM proteins
title_sort Feedback modulation of Orai1α and Orai1β protein content mediated by STIM proteins
dc.creator.none.fl_str_mv Nieto-Felipe, Joel
Macías-Diaz, Álvaro
Jiménez-Velarde, Vanesa
López, José J.
Salido, Gines M.
Smani, Tarik
Jardín, Isaac
Rosado, Juan A.
author Nieto-Felipe, Joel
author_facet Nieto-Felipe, Joel
Macías-Diaz, Álvaro
Jiménez-Velarde, Vanesa
López, José J.
Salido, Gines M.
Smani, Tarik
Jardín, Isaac
Rosado, Juan A.
author_role author
author2 Macías-Diaz, Álvaro
Jiménez-Velarde, Vanesa
López, José J.
Salido, Gines M.
Smani, Tarik
Jardín, Isaac
Rosado, Juan A.
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Nieto-Felipe, Joel [0000-0001-6342-3893]
Smani, Tarik [0000-0002-1877-7438]
Jardín, Isaac [0000-0003-4575-8264]
Rosado, Juan A. [0000-0002-9749-2325]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Orai1α
Orai1β
STIM1
STIM2
Store‐operated Ca2+ entry
topic Orai1α
Orai1β
STIM1
STIM2
Store‐operated Ca2+ entry
description Store-operated Ca2+ entry is a mechanism controlled by the filling state of the intracellular Ca2+ stores, predominantly the endoplasmic reticulum (ER), where ER-resident proteins STIM1 and STIM2 orchestrate the activation of Orai channels in the plasma membrane, and Orai1 playing a predominant role. Two forms of Orai1, Orai1α and Orai1β, have been identified, which arises the question whether they are equally regulated by STIM proteins. We demonstrate that STIM1 preferentially activates Orai1α over STIM2, yet both STIM proteins similarly activate Orai1β. Under resting conditions, there is a pronounced association between STIM2 and Orai1α. STIM1 and STIM2 are also shown to influence the protein levels of the Orai1 variants, independently of Ca2+ influx, via lysosomal degradation. Interestingly, Orai1α and Orai1β appear to selectively regulate the protein level of STIM1, but not STIM2. These observations offer crucial insights into the regulatory dynamics between STIM proteins and Orai1 variants, enhancing our understanding of the intricate processes that fine-tune intracellular Ca2+ signaling.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/390850
https://api.elsevier.com/content/abstract/scopus_id/85205541665
url http://hdl.handle.net/10261/390850
https://api.elsevier.com/content/abstract/scopus_id/85205541665
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.1002/jcp.31450
https://doi.org/10.1002/jcp.31450
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv John Wiley & Sons
publisher.none.fl_str_mv John Wiley & Sons
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.811543

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