Dynamic interaction of SARAF with STIM1 and Orai1 to modulate store-operated calcium entry

Ca2+ influx by store-operated Ca2+ channels is a major mechanism for intracellular Ca2+ homeostasis and cellular function. Here we present evidence for the dynamic interaction between the SOCE-associated regulatory factor (SARAF), STIM1 and Orai1. SARAF overexpression attenuated SOCE and the STIM1-O...

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Authors: Albarrán, Letizia, López, José J., Ben Amor, Nidhal, Martín-Cano, Francisco E., Berna-Erro, Alejandro, Smani, Tarik, Salido, Ginés M., Rosado, Juan A.
Format: article
Status:Published version
Publication Date:2016
Country:España
Institution:Consejo Superior de Investigaciones Científicas (CSIC)
Repository:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/181372
Online Access:http://hdl.handle.net/10261/181372
Access Level:Open access
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spelling Dynamic interaction of SARAF with STIM1 and Orai1 to modulate store-operated calcium entryAlbarrán, LetiziaLópez, José J.Ben Amor, NidhalMartín-Cano, Francisco E.Berna-Erro, AlejandroSmani, TarikSalido, Ginés M.Rosado, Juan A.Ca2+ influx by store-operated Ca2+ channels is a major mechanism for intracellular Ca2+ homeostasis and cellular function. Here we present evidence for the dynamic interaction between the SOCE-associated regulatory factor (SARAF), STIM1 and Orai1. SARAF overexpression attenuated SOCE and the STIM1-Orai1 interaction in cells endogenously expressing STIM1 and Orai1 while RNAi-mediated SARAF silencing induced opposite effects. SARAF impaired the association between Orai1 and the Orai1-activating small fragment of STIM1 co-expressed in the STIM1-deficient NG115-401L cells. Cell treatment with thapsigargin or physiological agonists results in direct association of SARAF with Orai1. STIM1-independent interaction of SARAF with Orai1 leads to activation of this channel. In cells endogenously expressing STIM1 and Orai1, Ca2+ store depletion leads to dissociation of SARAF with STIM1 approximately 30s after treatment with thapsigargin, which paralleled the increase in SARAF-Orai1 interaction, followed by reinteraction with STIM1 and dissociation from Orai1. Co-expression of SARAF and either Orai1 or various N-terminal deletion Orai1 mutants did not alter SARAF-Orai1 interaction; however, expression of C-terminal deletion Orai1 mutants or blockade of the C-terminus of Orai1 impair the interaction with SARAF. These observations suggest that SARAF exerts an initial positive role in the activation of SOCE followed by the facilitation of SCDI of Orai1.Supported by MINECO (Grants BFU2013-45564-C2-1-P, BFU2013-45564-C2-2-P, BFU2011-24365 and RD12-0043-0016 (RETICEF)) and Junta de Extremadura-FEDER. JJL and LA are supported by Juan de la Cierva Program and MINECO fellowship BES-2011-043356, respectively.Peer reviewedSpringer NatureMinisterio de Economía y Competitividad (España)European CommissionJunta de ExtremaduraRed Temática de Investigación Cooperativa en Envejecimiento y Fragilidad (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]201920192016info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/181372reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2013-45564-C2-1-Pinfo:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2013-45564-C2-2-Phttps://doi.org/10.1038/srep24452Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1813722026-05-22T06:33:51Z
dc.title.none.fl_str_mv Dynamic interaction of SARAF with STIM1 and Orai1 to modulate store-operated calcium entry
title Dynamic interaction of SARAF with STIM1 and Orai1 to modulate store-operated calcium entry
spellingShingle Dynamic interaction of SARAF with STIM1 and Orai1 to modulate store-operated calcium entry
Albarrán, Letizia
title_short Dynamic interaction of SARAF with STIM1 and Orai1 to modulate store-operated calcium entry
title_full Dynamic interaction of SARAF with STIM1 and Orai1 to modulate store-operated calcium entry
title_fullStr Dynamic interaction of SARAF with STIM1 and Orai1 to modulate store-operated calcium entry
title_full_unstemmed Dynamic interaction of SARAF with STIM1 and Orai1 to modulate store-operated calcium entry
title_sort Dynamic interaction of SARAF with STIM1 and Orai1 to modulate store-operated calcium entry
dc.creator.none.fl_str_mv Albarrán, Letizia
López, José J.
Ben Amor, Nidhal
Martín-Cano, Francisco E.
Berna-Erro, Alejandro
Smani, Tarik
Salido, Ginés M.
Rosado, Juan A.
author Albarrán, Letizia
author_facet Albarrán, Letizia
López, José J.
Ben Amor, Nidhal
Martín-Cano, Francisco E.
Berna-Erro, Alejandro
Smani, Tarik
Salido, Ginés M.
Rosado, Juan A.
author_role author
author2 López, José J.
Ben Amor, Nidhal
Martín-Cano, Francisco E.
Berna-Erro, Alejandro
Smani, Tarik
Salido, Ginés M.
Rosado, Juan A.
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
European Commission
Junta de Extremadura
Red Temática de Investigación Cooperativa en Envejecimiento y Fragilidad (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
description Ca2+ influx by store-operated Ca2+ channels is a major mechanism for intracellular Ca2+ homeostasis and cellular function. Here we present evidence for the dynamic interaction between the SOCE-associated regulatory factor (SARAF), STIM1 and Orai1. SARAF overexpression attenuated SOCE and the STIM1-Orai1 interaction in cells endogenously expressing STIM1 and Orai1 while RNAi-mediated SARAF silencing induced opposite effects. SARAF impaired the association between Orai1 and the Orai1-activating small fragment of STIM1 co-expressed in the STIM1-deficient NG115-401L cells. Cell treatment with thapsigargin or physiological agonists results in direct association of SARAF with Orai1. STIM1-independent interaction of SARAF with Orai1 leads to activation of this channel. In cells endogenously expressing STIM1 and Orai1, Ca2+ store depletion leads to dissociation of SARAF with STIM1 approximately 30s after treatment with thapsigargin, which paralleled the increase in SARAF-Orai1 interaction, followed by reinteraction with STIM1 and dissociation from Orai1. Co-expression of SARAF and either Orai1 or various N-terminal deletion Orai1 mutants did not alter SARAF-Orai1 interaction; however, expression of C-terminal deletion Orai1 mutants or blockade of the C-terminus of Orai1 impair the interaction with SARAF. These observations suggest that SARAF exerts an initial positive role in the activation of SOCE followed by the facilitation of SCDI of Orai1.
publishDate 2016
dc.date.none.fl_str_mv 2016
2019
2019
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/10261/181372
url http://hdl.handle.net/10261/181372
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2013-45564-C2-1-P
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2013-45564-C2-2-P
https://doi.org/10.1038/srep24452
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
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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