Author response: Epithelial magnesium transport by TRPM6 is essential for prenatal development and adult survival

Chubanov, Vladimir; Ferioli, Silvia; Wisnowsky, Annika; Simmons, David G.; Leitzinger, Christin; Einer, Claudia; Jonas, Wenke; Shymkiv, Yuriy; Bartsch, Harald; Braun, Attila; Akdogan, Banu; Mittermeier, Lorenz; Sytik, Ludmila; Friedrich, Torben; Jurinović, Vindi; Vorst, Emiel Pc van der; Yildirim, Önder; Sotlar, Karl; Schürmann, Annette; Zierler, Susanna; Zischka, Hans; Ryazanov, Alexey G.; Gudermann, Thomas

doi:10.7554/elife.20914.030

Cited by 1 publication

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“…In some TRPM7-APs from HEK293 cells, we detected TRPM6, a genetically related channel, and two proteins representing the gene family of Phosphatase of Regenerating Liver 1 and 3 (PRL1, 3; also entitled Protein tyrosine phosphatases type 4A1 and 3, PTP4A1 and 3) (Table 1). The Mg 2+ transporter protein TRPM6 has been described to physically and functionally interact with TRPM7 (6,49,50 (26). Briefly, rabbits were immunised with a phosphorylated peptide H2N-DSPEVD(p)SKAALLPC-NH2 coupled via its C-terminal cysteine residue to keyhole limpet hemocyanin (Eurogentec, Belgium).…”

Section: Discussionmentioning

confidence: 99%

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

Kollewe

Chubanov²,

Tseung³

et al. 2021

Preprint

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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 StatementHigh-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.

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