Referenced in: none

Automatically associated channels: TRP , TRPM , TRPM5

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

Authors: Sandra Mitrovic, Cristina Nogueira, Gerard Cantero-Recasens, Kerstin Kiefer, José M Fernández-Fernández, Jean-François Popoff, Laetitia Casano, Frederic A Bard, Raul Gomez, Miguel A Valverde, Vivek Malhotra

Journal, date & volume: Elife, 2013 , 2, e00658

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23741618

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. DOI:http://dx.doi.org/10.7554/eLife.00658.001.