Functional Characterization of Homo- and Heteromeric Channel Kinases TRPM6 and TRPM7

TRPM6 and TRPM7 are two known channel kinases that play important roles in various physiological processes, including Mg2+ homeostasis. Mutations in TRPM6 cause hereditary hypomagnesemia and secondary hypocalcemia (HSH). However, whether TRPM6 encodes functional channels is controversial. Here we de...

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Main Authors:	Li, Mingjiang, Jiang, Jianmin, Yue, Lixia
Format:	Online
Language:	English
Published:	The Rockefeller University Press 2006
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2151519/

id	pubmed-2151519
recordtype	oai_dc
spelling	pubmed-21515192008-01-17 Functional Characterization of Homo- and Heteromeric Channel Kinases TRPM6 and TRPM7 Li, Mingjiang Jiang, Jianmin Yue, Lixia Articles TRPM6 and TRPM7 are two known channel kinases that play important roles in various physiological processes, including Mg2+ homeostasis. Mutations in TRPM6 cause hereditary hypomagnesemia and secondary hypocalcemia (HSH). However, whether TRPM6 encodes functional channels is controversial. Here we demonstrate several signature features of TRPM6 that distinguish TRPM6 from TRPM7 and TRPM6/7 channels. We show that heterologous expression of TRPM6 but not the mutant TRPM6S141L produces functional channels with divalent cation permeability profile and pH sensitivity distinctive from those of TRPM7 channels and TRPM6/7 complexes. TRPM6 exhibits unique unitary conductance that is 2- and 1.5-fold bigger than that of TRPM7 and TRPM6/7. Moreover, micromolar levels of 2-aminoethoxydiphenyl borate (2-APB) maximally increase TRPM6 but significantly inhibit TRPM7 channel activities; whereas millimolar concentrations of 2-APB potentiate TRPM6/7 and TRPM7 channel activities. Furthermore, Mg2+ and Ca2+ entry through TRPM6 is enhanced three- to fourfold by 2-APB. Collectively, these results indicate that TRPM6 forms functional homomeric channels as well as heteromeric TRPM6/7 complexes. The unique characteristics of these three channel types, TRPM6, TRPM7, and TRPM6/7, suggest that they may play different roles in vivo. The Rockefeller University Press 2006-05 /pmc/articles/PMC2151519/ /pubmed/16636202 http://dx.doi.org/10.1085/jgp.200609502 Text en Copyright © 2006, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Li, Mingjiang Jiang, Jianmin Yue, Lixia
spellingShingle	Li, Mingjiang Jiang, Jianmin Yue, Lixia Functional Characterization of Homo- and Heteromeric Channel Kinases TRPM6 and TRPM7
author_facet	Li, Mingjiang Jiang, Jianmin Yue, Lixia
author_sort	Li, Mingjiang
title	Functional Characterization of Homo- and Heteromeric Channel Kinases TRPM6 and TRPM7
title_short	Functional Characterization of Homo- and Heteromeric Channel Kinases TRPM6 and TRPM7
title_full	Functional Characterization of Homo- and Heteromeric Channel Kinases TRPM6 and TRPM7
title_fullStr	Functional Characterization of Homo- and Heteromeric Channel Kinases TRPM6 and TRPM7
title_full_unstemmed	Functional Characterization of Homo- and Heteromeric Channel Kinases TRPM6 and TRPM7
title_sort	functional characterization of homo- and heteromeric channel kinases trpm6 and trpm7
description	TRPM6 and TRPM7 are two known channel kinases that play important roles in various physiological processes, including Mg2+ homeostasis. Mutations in TRPM6 cause hereditary hypomagnesemia and secondary hypocalcemia (HSH). However, whether TRPM6 encodes functional channels is controversial. Here we demonstrate several signature features of TRPM6 that distinguish TRPM6 from TRPM7 and TRPM6/7 channels. We show that heterologous expression of TRPM6 but not the mutant TRPM6S141L produces functional channels with divalent cation permeability profile and pH sensitivity distinctive from those of TRPM7 channels and TRPM6/7 complexes. TRPM6 exhibits unique unitary conductance that is 2- and 1.5-fold bigger than that of TRPM7 and TRPM6/7. Moreover, micromolar levels of 2-aminoethoxydiphenyl borate (2-APB) maximally increase TRPM6 but significantly inhibit TRPM7 channel activities; whereas millimolar concentrations of 2-APB potentiate TRPM6/7 and TRPM7 channel activities. Furthermore, Mg2+ and Ca2+ entry through TRPM6 is enhanced three- to fourfold by 2-APB. Collectively, these results indicate that TRPM6 forms functional homomeric channels as well as heteromeric TRPM6/7 complexes. The unique characteristics of these three channel types, TRPM6, TRPM7, and TRPM6/7, suggest that they may play different roles in vivo.
publisher	The Rockefeller University Press
publishDate	2006
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2151519/
_version_	1611424113755160576

Functional Characterization of Homo- and Heteromeric Channel Kinases TRPM6 and TRPM7

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