TRPM5-mediated calcium uptake regulates mucin secretion from human colon goblet cells

Mucin 5AC (MUC5AC) is secreted by goblet cells of the respiratory tract and, surprisingly, also expressed de novo in mucus secreting cancer lines. siRNA-mediated knockdown of 7343 human gene products in a human colonic cancer goblet cell line (HT29-18N2) revealed new proteins, including a Ca(2+)-act...

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Published in:eLife 2013-05, Vol.2, p.e00658
Main Authors: Mitrovic, Sandra, Nogueira, Cristina, Cantero-Recasens, Gerard, Kiefer, Kerstin, Fernández-Fernández, José M, Popoff, Jean-François, Casano, Laetitia, Bard, Frederic A, Gomez, Raul, Valverde, Miguel A, Malhotra, Vivek
Format: Article
Language:English
Subjects:
Calcium (extracellular)
Calcium - metabolism
Calcium influx
Calcium signalling
Cancer
Cell Biology
Colon
Colon - cytology
Colon - secretion
Colorectal cancer
Càncer
Developmental biology
Genètica
Goblet cells
Goblet Cells - cytology
Goblet Cells - secretion
Golgi apparatus
Golgi Apparatus - drug effects
Golgi Apparatus - metabolism
Humans
Inflammatory bowel disease
Kinases
Microscopy
Molecular weight
Mucin
Mucin5AC
Mucins - secretion
Mucus
Na+/Ca2+ exchanger
Physiology
Proteins
Proteïnes
Respiratory tract
Secretion
Secretory vesicles
siRNA
Tetradecanoylphorbol Acetate - pharmacology
Transient receptor potential proteins
TRPM Cation Channels - metabolism
TRPM Cation Channels - physiology
TRPM5
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Summary:Mucin 5AC (MUC5AC) is secreted by goblet cells of the respiratory tract and, surprisingly, also expressed de novo in mucus secreting cancer lines. siRNA-mediated knockdown of 7343 human gene products in a human colonic cancer goblet cell line (HT29-18N2) revealed new proteins, including a Ca(2+)-activated channel TRPM5, for MUC5AC secretion. TRPM5 was required for PMA and ATP-induced secretion of MUC5AC from the post-Golgi secretory granules. Stable knockdown of TRPM5 reduced a TRPM5-like current and ATP-mediated Ca(2+) signal. ATP-induced MUC5AC secretion depended strongly on Ca(2+) influx, which was markedly reduced in TRPM5 knockdown cells. The difference in ATP-induced Ca(2+) entry between control and TRPM5 knockdown cells was abrogated in the absence of extracellular Ca(2+) and by inhibition of the Na(+)/Ca(2+) exchanger (NCX). Accordingly, MUC5AC secretion was reduced by inhibition of NCX. Thus TRPM5 activation by ATP couples TRPM5-mediated Na(+) entry to promote Ca(2+) uptake via an NCX to trigger MUC5AC secretion. DOI:http://dx.doi.org/10.7554/eLife.00658.001.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.00658