Essential role for TRPM6 in epithelial magnesium transport and body magnesium homeostasis

  title={Essential role for TRPM6 in epithelial magnesium transport and body magnesium homeostasis},
  author={Vladimir Chubanov and Thomas Gudermann and Karl P. Schlingmann},
  journal={Pfl{\"u}gers Archiv},
Magnesium is an important cofactor for many biological processes such as protein synthesis, nucleic acid stability and neuromuscular excitability. The extracellular magnesium concentration is regulated tightly by the extent of intestinal absorption and renal excretion. Despite their critical role in magnesium handling, the molecular mechanisms mediating transepithelial transport are still not understood completely. Recently, genetic studies in patients with primary hypomagnesaemia and secondary… 

Vascular Biology of Magnesium: Implications in Cardiovascular Disease

Mg2+ deficiency results from reduced dietary intake, intestinal malabsorption, or renal loss, and transmembrane transport through ion channels and transporters.

Transient receptor potential melastatin 6 and 7 channels, magnesium transport, and vascular biology: implications in hypertension.

  • R. Touyz
  • Biology
    American journal of physiology. Heart and circulatory physiology
  • 2008
The importance of magnesium in vascular biology and implications in hypertension is discussed and the transport systems, particularly TRPM6 and TRPM7, which may play a role in the control of vascular magnesium homeostasis are highlighted.

Regulation of the Epithelial Mg2+ Channel TRPM6 by Estrogen and the Associated Repressor Protein of Estrogen Receptor Activity (REA)*

The repressor of estrogen receptor activity (REA) is identified as an interacting protein of TRPM6 that binds to the 6th, 7th, and 8th β-sheets in its α-kinase domain and provides new insight into the molecular mechanism of renal transepithelial Mg2+ transport.

Epithelial Ca2+ and Mg2+ channels in kidney disease.

This review updates the current knowledge and the recent advances of Ca2+ and Mg2+ reabsorption and related disorders.

SLC41A1 Is a Novel Mammalian Mg2+ Carrier*

It is demonstrated that human SLC41A1 overexpressed in HEK293 cells forms protein complexes and locates to the plasma membrane without, however, giving rise to any detectable magnesium currents during whole cell patch clamp experiments, which functionally identify SLC 41A1 as a mammalian carrier mediating magnesium efflux.

Vascular biology of magnesium and its transporters in hypertension.

The present review discusses the role of Mg2+ in vascular biology and implications in hypertension and focuses on the putative transport systems that control magnesium homeostasis in the vascular system.

Transient receptor potential melastatin 7 (TRPM7) cation channels, magnesium and the vascular system in hypertension.

Vascular TRPM7 has been implicated as a signaling kinase involved in vascular smooth muscle cell growth, apoptosis, adhesion, contraction, cytoskeletal organization and migration, and is modulated by vasoactive agents, pressure, stretch and osmotic changes.

Cellular magnesium homeostasis.

  • A. Romani
  • Biology
    Archives of biochemistry and biophysics
  • 2011

Relationship between low magnesium status and TRPM6 expression in the kidney and large intestine.

Dietary Mg(2+)-restriction results in increased M g(2+) (re)absorption, which is correlated with increased TRPM6 expression, and in MgL and MgH mice, the inherited Mg (2+) status is linked to different TRPM 6 expression.

Relationship between low magnesium status and TRPM 6 expression in the kidney and large intestine

The MgL and MgH mice respond differently to a low-Mg diet with regard to TRPM6 expression in the kidney, consistent with genetic factors contributing to the regulation of cellular Mg levels, and further studies of these mice strains could improve the understanding of the genetics of Mg homeostasis.



Insights into the molecular nature of magnesium homeostasis.

This review focuses on TRPM6, an ion channel of the "transient receptor potential (TRP) gene family, which, when mutated, causes a combined defect of intestinal magnesium absorption and renal magnesium conservation as observed in primary hypomagnesemia with secondary hypocalcemia.

TRPM6 Forms the Mg2+ Influx Channel Involved in Intestinal and Renal Mg2+ Absorption*

It is shown that TRPM6 is specifically localized along the apical membrane of the renal distal convoluted tubule and the brush-border membranes of the small intestine, epithelia particularly associated with active Mg2+ (re)absorption.

Renal magnesium handling: new insights in understanding old problems.

Patients with Bartter's and Gitelman's syndromes, diseases of salt transport in the loop and distal tubule, respectively, are associated with disturbances in renal magnesium handling and familial diseases associated with renal magnesium-wasting provide a unique opportunity to study these intrinsic controls.

Genetics of hereditary disorders of magnesium homeostasis

This review focuses on clinical and genetic aspects of hereditary disorders of magnesium homeostasis, including primary defects of epithelial magnesium transport, disorders associated with defects in Ca2+/ Mg2+ sensing, as well as diseases characterized by renal salt wasting and hypokalemic alkalosis, with special emphasis on disturbed magnesiumHomeostasis.

Regulation of Vertebrate Cellular Mg2+ Homeostasis by TRPM7

Hormonal regulation of Mg2+ transport and homeostasis in eukaryotic cells

The present review will attempt to provide a general framework to understand how cellular Mg2+ content and transport are regulated in eukaryotic cells, and how changes in cellular and plasma Mg 2+ content contribute to a physiological regulation of intracellular and extracellular enzymes.

Disruption of TRPM6/TRPM7 complex formation by a mutation in the TRPM6 gene causes hypomagnesemia with secondary hypocalcemia.

The naturally occurring S141L TRPM 6 missense mutation abrogated the oligomeric assembly of TRPM6, thus providing a cell biological explanation for the human disease.

Identification and characterization of a novel mammalian Mg2+ transporter with channel-like properties

It is suggested that MagT1 may provide a selective and regulated pathway for Mg2+ transport in epithelial cells and in kidney cortex of mice maintained on low magnesium diets compared to those animals consuming normal diets.

Current understanding of mammalian TRP homologues.