The molecular appearance of native TRPM7 channel complexes identified by high-resolution proteomics.

Autor:	Kollewe A; Institute of Physiology II, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Chubanov V; Walther-Straub Institute of Pharmacology and Toxicology, LMU Munich, Munich, Germany., Tseung FT; Walther-Straub Institute of Pharmacology and Toxicology, LMU Munich, Munich, Germany., Correia L; Walther-Straub Institute of Pharmacology and Toxicology, LMU Munich, Munich, Germany., Schmidt E; Walther-Straub Institute of Pharmacology and Toxicology, LMU Munich, Munich, Germany., Rössig A; Walther-Straub Institute of Pharmacology and Toxicology, LMU Munich, Munich, Germany., Zierler S; Walther-Straub Institute of Pharmacology and Toxicology, LMU Munich, Munich, Germany.; Institute of Pharmacology, Johannes Kepler University Linz, Linz, Austria., Haupt A; Institute of Physiology II, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Müller CS; Institute of Physiology II, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Bildl W; Institute of Physiology II, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Schulte U; Institute of Physiology II, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; Signalling Research Centres BIOSS and CIBSS, Freiburg, Germany., Nicke A; Walther-Straub Institute of Pharmacology and Toxicology, LMU Munich, Munich, Germany., Fakler B; Institute of Physiology II, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; Signalling Research Centres BIOSS and CIBSS, Freiburg, Germany., Gudermann T; Walther-Straub Institute of Pharmacology and Toxicology, LMU Munich, Munich, Germany.; German Center for Lung Research, Munich, Germany.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2021 Nov 12; Vol. 10. Date of Electronic Publication: 2021 Nov 12.
DOI:	10.7554/eLife.68544
Abstrakt:	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. Competing Interests: AK, VC, FT, LC, ES, AR, SZ, AH, CM, WB, US, AN, BF, TG No competing interests declared (© 2021, Kollewe et al.)
Databáze:	MEDLINE
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