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

Mitrovic, Sandra; Nogueira, Cristina; Cantero Recasens, Gerard, 1984-; Kiefer, Kerstin, 1986-; Fernández-Fernández, José Manuel, 1967-; Popoff, Jean-François; Casano, Laetitia; Bard, Frederic A.; Gómez, Raul; Valverde, M. A. (Miguel Ángel), 1963-; Malhotra, Vivek

doi:http://dx.doi.org/10.7554/eLife.00658

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

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Mitrovic S, Nogueira C, Cantero-Recasens G, Kiefer K, Fernández-Fernández JM, Popoff JF et al. TRPM5-mediated calcium uptake regulates mucin secretion from human colon goblet cells. Elife. 2013;2:e00658. DOI: 10.7554/eLife.00658

Abstract

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