TRPM6 is Essential for Magnesium Uptake and Epithelial Cell Function in the Colon
Intestinal magnesium (Mg) uptake is essential for systemic Mg homeostasis. Colon cells express the two highly homologous transient receptor potential melastatin type (TRPM) 6 and 7 Mg2+ channels, but their precise function and the consequences of their mutual interaction are not clear. To explore th...
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doaj-8be5aa829c5d40f8ac70c80be98ad01a2020-11-24T23:46:04ZengMDPI AGNutrients2072-66432018-06-0110678410.3390/nu10060784nu10060784TRPM6 is Essential for Magnesium Uptake and Epithelial Cell Function in the ColonFrancesca Luongo0Giuseppe Pietropaolo1Mathieu Gautier2Isabelle Dhennin-Duthille3Halima Ouadid-Ahidouch4Federica I. Wolf5Valentina Trapani6Istituto di Patologia Generale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, I-00168 Rome, ItalyIstituto di Patologia Generale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, I-00168 Rome, ItalyLaboratoire de Physiologie Cellulaire et Moléculaire-EA4667, UFR Sciences, Université de Picardie Jules Verne, F-80039 Amiens, FranceLaboratoire de Physiologie Cellulaire et Moléculaire-EA4667, UFR Sciences, Université de Picardie Jules Verne, F-80039 Amiens, FranceLaboratoire de Physiologie Cellulaire et Moléculaire-EA4667, UFR Sciences, Université de Picardie Jules Verne, F-80039 Amiens, FranceIstituto di Patologia Generale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, I-00168 Rome, ItalyIstituto di Patologia Generale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, I-00168 Rome, ItalyIntestinal magnesium (Mg) uptake is essential for systemic Mg homeostasis. Colon cells express the two highly homologous transient receptor potential melastatin type (TRPM) 6 and 7 Mg2+ channels, but their precise function and the consequences of their mutual interaction are not clear. To explore the functional role of TRPM6 and TRPM7 in the colon, we used human colon cell lines that innately express both channels and analyzed the functional consequences of genetic knocking-down, by RNA interference, or pharmacological inhibition, by NS8593, of either channel. TRPM7 silencing caused an increase in Mg2+ influx, and correspondingly enhanced cell proliferation and migration, while downregulation of TRPM6 did not affect significantly either Mg2+ influx or cell proliferation. Exposure to the specific TRPM6/7 inhibitor NS8593 reduced Mg2+ influx, and consequently cell proliferation and migration, but Mg supplementation rescued the inhibition. We propose a model whereby in colon cells the functional Mg2+ channel at the plasma membrane may consist of both TRPM7 homomers and TRPM6/7 heteromers. A different expression ratio between the two proteins may result in different functional properties. Altogether, our findings confirm that TRPM6 cannot be replaced by TRPM7, and that TRPM6/7 complexes and TRPM6/7-mediated Mg2+ influx are indispensable in human epithelial colon cells.http://www.mdpi.com/2072-6643/10/6/784cell migrationcell proliferationintestineion imagingmagnesium channelmagnesium homeostasisMagT1NS8593TRPM7wound healing |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Francesca Luongo Giuseppe Pietropaolo Mathieu Gautier Isabelle Dhennin-Duthille Halima Ouadid-Ahidouch Federica I. Wolf Valentina Trapani |
spellingShingle |
Francesca Luongo Giuseppe Pietropaolo Mathieu Gautier Isabelle Dhennin-Duthille Halima Ouadid-Ahidouch Federica I. Wolf Valentina Trapani TRPM6 is Essential for Magnesium Uptake and Epithelial Cell Function in the Colon Nutrients cell migration cell proliferation intestine ion imaging magnesium channel magnesium homeostasis MagT1 NS8593 TRPM7 wound healing |
author_facet |
Francesca Luongo Giuseppe Pietropaolo Mathieu Gautier Isabelle Dhennin-Duthille Halima Ouadid-Ahidouch Federica I. Wolf Valentina Trapani |
author_sort |
Francesca Luongo |
title |
TRPM6 is Essential for Magnesium Uptake and Epithelial Cell Function in the Colon |
title_short |
TRPM6 is Essential for Magnesium Uptake and Epithelial Cell Function in the Colon |
title_full |
TRPM6 is Essential for Magnesium Uptake and Epithelial Cell Function in the Colon |
title_fullStr |
TRPM6 is Essential for Magnesium Uptake and Epithelial Cell Function in the Colon |
title_full_unstemmed |
TRPM6 is Essential for Magnesium Uptake and Epithelial Cell Function in the Colon |
title_sort |
trpm6 is essential for magnesium uptake and epithelial cell function in the colon |
publisher |
MDPI AG |
series |
Nutrients |
issn |
2072-6643 |
publishDate |
2018-06-01 |
description |
Intestinal magnesium (Mg) uptake is essential for systemic Mg homeostasis. Colon cells express the two highly homologous transient receptor potential melastatin type (TRPM) 6 and 7 Mg2+ channels, but their precise function and the consequences of their mutual interaction are not clear. To explore the functional role of TRPM6 and TRPM7 in the colon, we used human colon cell lines that innately express both channels and analyzed the functional consequences of genetic knocking-down, by RNA interference, or pharmacological inhibition, by NS8593, of either channel. TRPM7 silencing caused an increase in Mg2+ influx, and correspondingly enhanced cell proliferation and migration, while downregulation of TRPM6 did not affect significantly either Mg2+ influx or cell proliferation. Exposure to the specific TRPM6/7 inhibitor NS8593 reduced Mg2+ influx, and consequently cell proliferation and migration, but Mg supplementation rescued the inhibition. We propose a model whereby in colon cells the functional Mg2+ channel at the plasma membrane may consist of both TRPM7 homomers and TRPM6/7 heteromers. A different expression ratio between the two proteins may result in different functional properties. Altogether, our findings confirm that TRPM6 cannot be replaced by TRPM7, and that TRPM6/7 complexes and TRPM6/7-mediated Mg2+ influx are indispensable in human epithelial colon cells. |
topic |
cell migration cell proliferation intestine ion imaging magnesium channel magnesium homeostasis MagT1 NS8593 TRPM7 wound healing |
url |
http://www.mdpi.com/2072-6643/10/6/784 |
work_keys_str_mv |
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