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Elife. 2018 Oct 1;7. pii: e39729. doi: 10.7554/eLife.39729.

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

Author information

1
Centre for Genomic Regulation, The Barcelona Institute of Science and Technology, Barcelona, Spain.
2
Laboratory of Molecular Physiology and Channelopathies, Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona, Spain.
3
Spanish Network for Biomedical Research in Neurodegenerative Diseases, Madrid, Spain.
4
National Biotechnology Center, Madrid, Spain.
5
Universitat Pompeu Fabra, Barcelona, Spain.
6
Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain.

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.

Editorial note:

This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).

KEYWORDS:

KChIP3; MUC5AC granules; baseline mucin secretion; calcium oscillations; calcium sensor; cell biology; human; mouse

PMID:
30272559
PMCID:
PMC6167051
DOI:
10.7554/eLife.39729
[Indexed for MEDLINE]
Free PMC Article

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