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The molecular appearance of native TRPM7 channel complexes identified by high-resolution proteomics
The transient receptor potential melastatin-subfamily member 7 (TRPM7) is a ubiquitously expressed membrane protein consisting of ion channel and protein kinase domains. TRPM7 plays a fundamental role in the cellular uptake of divalent cations such as Zn(2+), Mg(2+), and Ca(2+), and thus shapes cell...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8616561/ https://www.ncbi.nlm.nih.gov/pubmed/34766907 http://dx.doi.org/10.7554/eLife.68544 |
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author | Kollewe, Astrid Chubanov, Vladimir Tseung, Fong Tsuen Correia, Leonor Schmidt, Eva Rössig, Anna Zierler, Susanna Haupt, Alexander Müller, Catrin Swantje Bildl, Wolfgang Schulte, Uwe Nicke, Annette Fakler, Bernd Gudermann, Thomas |
author_facet | Kollewe, Astrid Chubanov, Vladimir Tseung, Fong Tsuen Correia, Leonor Schmidt, Eva Rössig, Anna Zierler, Susanna Haupt, Alexander Müller, Catrin Swantje Bildl, Wolfgang Schulte, Uwe Nicke, Annette Fakler, Bernd Gudermann, Thomas |
author_sort | Kollewe, Astrid |
collection | PubMed |
description | The transient receptor potential melastatin-subfamily member 7 (TRPM7) is a ubiquitously expressed membrane protein consisting of ion channel and protein kinase domains. TRPM7 plays a fundamental role in the cellular uptake of divalent cations such as Zn(2+), Mg(2+), and Ca(2+), and thus shapes cellular excitability, plasticity, and metabolic activity. The molecular appearance and operation of TRPM7 channels in native tissues have remained unresolved. Here, we investigated the subunit composition of endogenous TRPM7 channels in rodent brain by multi-epitope affinity purification and high-resolution quantitative mass spectrometry (MS) analysis. We found that native TRPM7 channels are high-molecular-weight multi-protein complexes that contain the putative metal transporter proteins CNNM1-4 and a small G-protein ADP-ribosylation factor-like protein 15 (ARL15). Heterologous reconstitution experiments confirmed the formation of TRPM7/CNNM/ARL15 ternary complexes and indicated that complex formation effectively and specifically impacts TRPM7 activity. These results open up new avenues towards a mechanistic understanding of the cellular regulation and function of TRPM7 channels. |
format | Online Article Text |
id | pubmed-8616561 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-86165612021-11-26 The molecular appearance of native TRPM7 channel complexes identified by high-resolution proteomics Kollewe, Astrid Chubanov, Vladimir Tseung, Fong Tsuen Correia, Leonor Schmidt, Eva Rössig, Anna Zierler, Susanna Haupt, Alexander Müller, Catrin Swantje Bildl, Wolfgang Schulte, Uwe Nicke, Annette Fakler, Bernd Gudermann, Thomas eLife Biochemistry and Chemical Biology The transient receptor potential melastatin-subfamily member 7 (TRPM7) is a ubiquitously expressed membrane protein consisting of ion channel and protein kinase domains. TRPM7 plays a fundamental role in the cellular uptake of divalent cations such as Zn(2+), Mg(2+), and Ca(2+), and thus shapes cellular excitability, plasticity, and metabolic activity. The molecular appearance and operation of TRPM7 channels in native tissues have remained unresolved. Here, we investigated the subunit composition of endogenous TRPM7 channels in rodent brain by multi-epitope affinity purification and high-resolution quantitative mass spectrometry (MS) analysis. We found that native TRPM7 channels are high-molecular-weight multi-protein complexes that contain the putative metal transporter proteins CNNM1-4 and a small G-protein ADP-ribosylation factor-like protein 15 (ARL15). Heterologous reconstitution experiments confirmed the formation of TRPM7/CNNM/ARL15 ternary complexes and indicated that complex formation effectively and specifically impacts TRPM7 activity. These results open up new avenues towards a mechanistic understanding of the cellular regulation and function of TRPM7 channels. eLife Sciences Publications, Ltd 2021-11-12 /pmc/articles/PMC8616561/ /pubmed/34766907 http://dx.doi.org/10.7554/eLife.68544 Text en © 2021, Kollewe et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Biochemistry and Chemical Biology Kollewe, Astrid Chubanov, Vladimir Tseung, Fong Tsuen Correia, Leonor Schmidt, Eva Rössig, Anna Zierler, Susanna Haupt, Alexander Müller, Catrin Swantje Bildl, Wolfgang Schulte, Uwe Nicke, Annette Fakler, Bernd Gudermann, Thomas The molecular appearance of native TRPM7 channel complexes identified by high-resolution proteomics |
title | The molecular appearance of native TRPM7 channel complexes identified by high-resolution proteomics |
title_full | The molecular appearance of native TRPM7 channel complexes identified by high-resolution proteomics |
title_fullStr | The molecular appearance of native TRPM7 channel complexes identified by high-resolution proteomics |
title_full_unstemmed | The molecular appearance of native TRPM7 channel complexes identified by high-resolution proteomics |
title_short | The molecular appearance of native TRPM7 channel complexes identified by high-resolution proteomics |
title_sort | molecular appearance of native trpm7 channel complexes identified by high-resolution proteomics |
topic | Biochemistry and Chemical Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8616561/ https://www.ncbi.nlm.nih.gov/pubmed/34766907 http://dx.doi.org/10.7554/eLife.68544 |
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