ArticleProceedings of the National Academy of Sciences of the United States of America2023
PRL-1/2 phosphatases control TRPM7 magnesium-dependent function to regulate cellular bioenergetics.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 22 citations in OpenAlex.
- Article
- Phosphatases of regenerating liver downregulate PTEN to promote tumorigenesis.Biochemical Society transactions · 2026Review
- S-acylation and membrane localization of the small GTPase ARL15 are mediated by the Golgi S-acyltransferases ZDHHC7 and ZDHHC3.The Journal of biological chemistry · 2026Article
- Leishmania donovani's protein tyrosine phosphatases interact with DUF21 and respond to environmental magnesium.The FEBS journal · 2026Article
- TRPM7 and magnesium orchestrate human CD4 T-cell activation and differentiation.Life science alliance · 2026Article
- The SLC-ome of membrane transport: From molecular discovery to physiology and clinical applications.Physiological reviews · 2025Review
- microRNAs Regulate Cellular Magnesium by Tuning Expression of the Plasma Membrane Protein CNNM4.ACS chemical biology · 2025Article
- Metal-modulated T cell antitumor immunity and emerging metalloimmunotherapy.Cancer metastasis reviews · 2025Review
- PRL2 negatively regulates FcεRI mediated activation of mast cells.Cell death & disease · 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
- Article
- Unlocking TRPM7 interactions: A database-driven quest.Computational and structural biotechnology journal · 2025Review
- Magnesium biology.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024Review
- Pathogenic heterozygous TRPM7 variants and hypomagnesemia with developmental delay.Clinical kidney journal · 2024Article
- Protein Tyrosine Phosphatase PRL-3: A Key Player in Cancer Signaling.Biomolecules · 2024Review
- Dimerization of the CNNM extracellular domain.Protein science : a publication of the Protein Society · 2024Article
- 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
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Phosphatases of regenerating liver (PRL-1, PRL-2, PRL-3; also known as PTP4A1, PTP4A2, PTP4A3, respectively) control intracellular magnesium levels by interacting with the CNNM magnesium transport regulators. Still, the exact mechanism governing magnesium transport by this protein complex is not well understood. Herein, we have developed a genetically encoded intracellular magnesium-specific reporter and demonstrate that the CNNM family inhibits the function of the TRPM7 magnesium channel. We show that the small GTPase ARL15 increases CNNM3/TRPM7 protein complex formation to reduce TRPM7 activity. Conversely, PRL-2 overexpression counteracts ARL15 binding to CNNM3 and enhances the function of TRPM7 by preventing the interaction between CNNM3 and TRPM7. Moreover, while TRPM7-induced cell signaling is promoted by PRL-1/2, it is reduced when CNNM3 is overexpressed. Lowering cellular magnesium levels reduces the interaction of CNNM3 with TRPM7 in a PRL-dependent manner, whereby knockdown of PRL-1/2 restores the protein complex formation. Cotargeting of TRPM7 and PRL-1/2 alters mitochondrial function and sensitizes cells to metabolic stress induced by magnesium depletion. These findings reveal the dynamic regulation of TRPM7 function in response to PRL-1/2 levels, to coordinate magnesium transport and reprogram cellular metabolism.
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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.