ArticlePLoS biology2021
CNNM proteins selectively bind to the TRPM7 channel to stimulate divalent cation entry into cells.
Article in PLoS biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Sperm Ion Transporters and Channels in Human Asthenozoospermia: Genetic Etiology, Lessons from Animal Models, and Clinical Perspectives.International journal of molecular sciences · 2022Pooled it
- Article
- TRPM7 and magnesium orchestrate human CD4 T-cell activation and differentiation.Life science alliance · 2026Article
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- The SLC-ome of membrane transport: From molecular discovery to physiology and clinical applications.Physiological reviews · 2025Review
- A distal convoluted tubule-specific isoform of murine SLC41A3 extrudes magnesium.Acta physiologica (Oxford, England) · 2025Article
- The PACT Network: PRL, ARL, CNNM, and TRPM Proteins in Magnesium Transport and Disease.International journal of molecular sciences · 2025Review
- TRPM7 channel activity promotes the pathogenesis of abdominal aortic aneurysms.Nature cardiovascular research · 2025Article
- Unlocking TRPM7 interactions: A database-driven quest.Computational and structural biotechnology journal · 2025Review
- Tuning fungal promoters for the expression of eukaryotic proteins.World journal of microbiology & biotechnology · 2024Review
- Article
- Magnesium Ion: A New Switch in Tumor Treatment.Biomedicines · 2024Review
- Pathogenic heterozygous TRPM7 variants and hypomagnesemia with developmental delay.Clinical kidney journal · 2024Article
- TRPM channels in health and disease.Nature reviews. Nephrology · 2024Review
- Dimerization of the CNNM extracellular domain.Protein science : a publication of the Protein Society · 2024Article
- Cleft palate and minor metabolic disturbances in a mouse global Arl15 gene knockout.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- Beyond Ion Homeostasis: Hypomagnesemia, Transient Receptor Potential Melastatin Channel 7, Mitochondrial Function, and Inflammation.Nutrients · 2023Article
- Phosphatase and Pseudo-Phosphatase Functions of Phosphatase of Regenerating Liver 3 (PRL-3) Are Insensitive to Divalent Metals In Vitro.ACS omega · 2023Article
- Structural insights into regulation of CNNM-TRPM7 divalent cation uptake by the small GTPase ARL15.eLife · 2023Article
- TRPM7 kinase mediates hypomagnesemia-induced seizure-related death.Scientific reports · 2023Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
Abstract
Magnesium is essential for cellular life, but how it is homeostatically controlled still remains poorly understood. Here, we report that members of CNNM family, which have been controversially implicated in both cellular Mg2+ influx and efflux, selectively bind to the TRPM7 channel to stimulate divalent cation entry into cells. Coexpression of CNNMs with the channel markedly increased uptake of divalent cations, which is prevented by an inactivating mutation to the channel's pore. Knockout (KO) of TRPM7 in cells or application of the TRPM7 channel inhibitor NS8593 also interfered with CNNM-stimulated divalent cation uptake. Conversely, KO of CNNM3 and CNNM4 in HEK-293 cells significantly reduced TRPM7-mediated divalent cation entry, without affecting TRPM7 protein expression or its cell surface levels. Furthermore, we found that cellular overexpression of phosphatases of regenerating liver (PRLs), known CNNMs binding partners, stimulated TRPM7-dependent divalent cation entry and that CNNMs were required for this activity. Whole-cell electrophysiological recordings demonstrated that deletion of CNNM3 and CNNM4 from HEK-293 cells interfered with heterologously expressed and native TRPM7 channel function. We conclude that CNNMs employ the TRPM7 channel to mediate divalent cation influx and that CNNMs also possess separate TRPM7-independent Mg2+ efflux activities that contribute to CNNMs' control of cellular Mg2+ homeostasis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.