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KChIP3 coupled to Ca2+ oscillations exerts a tonic brake on baseline mucin release in the colon

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dc.contributor.author Cantero Recasens, Gerard, 1984-
dc.contributor.author Butnaru, Cristian M.
dc.contributor.author Valverde, M. A. (Miguel Ángel), 1963-
dc.contributor.author Naranjo, José R.
dc.contributor.author Brouwers, Nathalie
dc.contributor.author Malhotra, Vivek
dc.date.accessioned 2019-02-08T08:40:58Z
dc.date.available 2019-02-08T08:40:58Z
dc.date.issued 2018
dc.identifier.citation Cantero-Recasens G, Butnaru CM, Valverde MA, Naranjo JR, Brouwers N, Malhotra V. KChIP3 coupled to Ca2+ oscillations exerts a tonic brake on baseline mucin release in the colon. eLife 2018;7:e39729. DOI: 10.7554/eLife.39729
dc.identifier.issn 2050-084X
dc.identifier.uri http://hdl.handle.net/10230/36537
dc.description.abstract Regulated mucin secretion from specialized goblet cells by exogenous agonist-dependent (stimulated) and -independent (baseline) manner is essential for the function of the epithelial lining. Over extended periods, baseline release of mucin can exceed quantities released by stimulated secretion, yet its regulation remains poorly characterized. We have discovered that ryanodine receptor-dependent intracellular Ca2+ oscillations effect the dissociation of the Ca2+-binding protein, KChIP3, encoded by KCNIP3 gene, from mature mucin-filled secretory granules, allowing for their exocytosis. Increased Ca2+ oscillations, or depleting KChIP3, lead to mucin hypersecretion in a human differentiated colonic cell line, an effect reproduced in the colon of Kcnip3-/- mice. Conversely, overexpressing KChIP3 or abrogating its Ca2+-sensing ability, increases KChIP3 association with granules, and inhibits baseline secretion. KChIP3 therefore emerges as the high-affinity Ca2+ sensor that negatively regulates baseline mucin secretion. We suggest KChIP3 marks mature, primed mucin granules, and functions as a Ca2+ oscillation-dependent brake to control baseline secretion.
dc.description.sponsorship This work was funded by grants from the Spanish Ministry of Economy and Competitiveness (BFU2013-44188-P to VM, SAF2015-69762R to MAV and SAF2017-89554-R to JRN) and FEDER Funds. We acknowledge support of the Spanish Ministry of Economy and Competitiveness, through the Programmes “Centro de Excelencia Severo Ochoa 2013- 2017” (SEV-2012-0208 & SEV-2013-0347) and Maria de Maeztu Units of Excellence in R&D (MDM-2015- 0502). This work reflects only the authors’ views, and the EU Community is not liable for any use that may be made of the information contained therein.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher eLife
dc.relation.ispartof eLife 2018;7:e39729
dc.rights © Cantero-Recasens et al. This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use and redistribution provided that the original author and source are credited.
dc.rights.uri https://creativecommons.org/licenses/by/4.0/
dc.title KChIP3 coupled to Ca2+ oscillations exerts a tonic brake on baseline mucin release in the colon
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.7554/eLife.39729
dc.subject.keyword KChIP3
dc.subject.keyword MUC5AC granules
dc.subject.keyword Baseline mucin secretion
dc.subject.keyword Calcium oscillations
dc.subject.keyword Calcium sensor
dc.subject.keyword Cell biology
dc.subject.keyword Human
dc.subject.keyword Mouse
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2013-44188-P
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2015-69762R
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2017-89554-R
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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