ArticleJournal of the American Society of Nephrology : JASN2016
Regulation of Mg2+ Reabsorption and Transient Receptor Potential Melastatin Type 6 Activity by cAMP Signaling.
Article in Journal of the American Society of Nephrology : JASN, 2016. 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, 25 citations in OpenAlex.
- Altered Magnesium Environments Restrict Colorectal HT-29 Spheroid Growth by Disturbing Cellular MgInternational journal of molecular sciences · 2026Article
- Sodium-glucose co-transporter 2 inhibitors are negatively correlated with hypomagnesemia in elderly patients with type 2 diabetes.Frontiers in nutrition · 2026Article
- Transient receptor potential melastatin 6 and transient receptor potential melastatin 6/7 antagonists suppress colon adenocarcinoma HT-29 cells.World journal of gastrointestinal oncology · 2025Article
- Magnesium biology.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024Review
- Ghrelin enhances tubular magnesium absorption in the kidney.Frontiers in physiology · 2024Article
- Hypomagnesemia and Cardiovascular Risk in Type 2 Diabetes.Endocrine reviews · 2023Article
- FAM111A is dispensable for electrolyte homeostasis in mice.Scientific reports · 2022Article
- Review
- Magnesium to prevent kidney disease-associated vascular calcification: crystal clear?Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2022Article
- Mass spectrometric analysis of TRPM6 and TRPM7 from small intestine of omeprazole-induced hypomagnesemic rats.Frontiers in oncology · 2022Article
- Adenylyl cyclase 3 regulates osteocyte mechanotransduction and primary cilium.Biochemical and biophysical research communications · 2021Article
- Effects of Quercetin on Acrylamide-Induced Variation of Serum Elements in Rats.Biological trace element research · 2021Article
- TRPM7 channel activity in Jurkat T lymphocytes during magnesium depletion and loading: implications for divalent metal entry and cytotoxicity.Pflugers Archiv : European journal of physiology · 2020Article
- Single-molecule labeling for studying trafficking of renal transporters.American journal of physiology. Renal physiology · 2018Review
- Genetics of Magnesium Disorders.Kidney diseases (Basel, Switzerland) · 2017Review
- A Novel Hypokalemic-Alkalotic Salt-Losing Tubulopathy in Patients withJournal of the American Society of Nephrology : JASN · 2017Article
- Identification of adenylyl cyclase isoforms mediating parathyroid hormone- and calcitonin-stimulated cyclic AMP accumulation in distal tubule cells.BMC nephrology · 2017Article
- Histone phosphorylation by TRPM6's cleaved kinase attenuates adjacent arginine methylation to regulate gene expression.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Role of renal TRP channels in physiology and pathology.Seminars in immunopathology · 2016Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
The transient receptor potential melastatin type 6 (TRPM6) epithelial Mg(2+) channels participate in transcellular Mg(2+) transport in the kidney and intestine. Previous reports suggested a hormonal cAMP-dependent regulation of Mg(2+) reabsorption in the kidney. The molecular details of this process are, however, unknown. Adenylate cyclase 3 (Adcy3) has been shown to colocalize with the Na(+)/Cl(-) cotransporter, a marker of the distal convoluted segment of the kidney, the principal site of TRPM6 expression. Given the critical role of TRPM6 in Mg(2+) reabsorption, an inducible kidney-specific Adcy3 deletion mouse model was characterized for blood and urinary electrolyte disturbances under a normal--and low--Mg(2+) diet. Increased urinary Mg(2+) wasting and Trpm6 mRNA levels were observed in the urine and kidney of Adcy3-deleted animals compared with wild-type controls. Serum Mg(2+) concentration was significantly lower in Adcy3-deleted animals at day 7 on the low Mg(2+) diet. Using patch clamp electrophysiology, cell surface biotinylation, and total internal reflection fluorescence live cell imaging of transfected HEK293 cells, we demonstrated that cAMP signaling rapidly potentiates TRPM6 activity by promoting TRPM6 accumulation at the plasma membrane and increasing its single-channel conductance. Comparison of electrophysiological data from cells expressing the phosphorylation-deficient S1252A or phosphomimetic S1252D TRPM6 mutants suggests that phosphorylation at this intracellular residue participates in the observed stimulation of channel activity. Altogether, these data support a physiologically relevant magnesiotropic role of cAMP signaling in the kidney by a direct stimulatory action of protein kinase A on the plasma membrane trafficking and function of TRPM6 ion channels.
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