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.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.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.doi http://dx.doi.org/10.7554/eLife.39729
- dc.identifier.issn 2050-084X
- dc.identifier.uri http://hdl.handle.net/10230/36537
- dc.language.iso eng
- dc.publisher eLife
- dc.relation.ispartof eLife 2018;7:e39729
- 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 © 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.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri https://creativecommons.org/licenses/by/4.0/
- 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.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.type.version info:eu-repo/semantics/publishedVersion