The rise and fall of novel renal magnesium transporters.

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Schaffers OJM, Hoenderop JGJ, Bindels RJM, de Baaij JHF

The rise and fall of novel renal magnesium transporters.

Am J Physiol Renal Physiol. 2018 Jun 1;314(6):F1027-F1033. doi: 10.1152/ajprenal.00634.2017. Epub 2018 Feb 7.

PubMed ID

29412701 [ View in PubMed

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Abstract

Body Mg(2+) balance is finely regulated in the distal convoluted tubule (DCT), where a tight interplay among transcellular reabsorption, mitochondrial exchange, and basolateral extrusion takes place. In the last decades, several research groups have aimed to identify the molecular players in these processes. A multitude of proteins have been proposed to function as Mg(2+) transporter in eukaryotes based on phylogenetic analysis, differential gene expression, and overexpression studies. However, functional evidence for many of these proteins is lacking. The aim of this review is, therefore, to critically reconsider all putative Mg(2+) transporters and put their presumed function in context of the renal handling of Mg(2+). Sufficient experimental evidence exists to acknowledge transient receptor potential melastatin (TRPM) 6 and TRPM7, solute carrier family 41 (SLC41) A1 and SLC41A3, and mitochondrial RNA splicing 2 (MRS2) as Mg(2+) transporters. TRPM6/7 facilitate Mg(2+) influx, SLC41A1 mediates Mg(2+) extrusion, and MRS2 and SLC41A3 are implicated in mitochondrial Mg(2+) homeostasis. These proteins are highly expressed in the DCT. The function of cyclin M (CNNM) proteins is still under debate. For the other proposed Mg(2+) transporters including Mg(2+) transporter subtype 1 (MagT1), nonimprinted in Prader-Willi/Angelman syndrome (NIPA), membrane Mg(2+) transport (MMgT), Huntingtin-interacting protein 14 (HIP14), and ATP13A4, functional evidence is limited, or functions alternative to Mg(2+) transport have been suggested. Additional characterization of their Mg(2+) transport proficiency should be provided before further claims about their role as Mg(2+) transporter can be made.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Magnesium	Magnesium transporter MRS2 homolog, mitochondrial	Protein	Humans	Unknown	Not Available	Details
Magnesium	Solute carrier family 41 member 1	Protein	Humans	Unknown	Not Available	Details
Magnesium	Solute carrier family 41 member 3	Protein	Humans	Unknown	Not Available	Details