RT Journal Article
SR Electronic
T1 The molecular appearance of native TRPM7 channel complexes identified by high-resolution proteomics
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.07.09.451738
DO 10.1101/2021.07.09.451738
A1 Astrid Kollewe
A1 Vladimir Chubanov
A1 Fong Tsuen Tseung
A1 Alexander Haupt
A1 Catrin Swantje Müller
A1 Wolfgang Bildl
A1 Uwe Schulte
A1 Annette Nicke
A1 Bernd Fakler
A1 Thomas Gudermann
YR 2021
UL http://biorxiv.org/content/early/2021/07/09/2021.07.09.451738.abstract
AB 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 Zn2+, Mg2+ and Ca2+, and thus shapes cellular excitability, plasticity and metabolic activity. The molecular appearance and operation of TRPM7 channel complexes 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 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 ARL15. Heterologous reconstitution experiments confirmed the formation of TRPM7/CNNM/ARL15 ternary complexes and indicated that ARL15 effectively and specifically impacts TRPM7 channel activity. These results open up new avenues towards a mechanistic understanding of the cellular regulation and function of TRPM7 channels.Impact Statement High-resolution proteomics in conjunction with biochemical and electrophysiological experiments revealed that the channel-kinase TRPM7 in the rodent brain forms macromolecular complexes containing the metal transporters CNNM1-4 and a small G protein ARL15.Competing Interest StatementThe authors have declared no competing interest.