SLC41 Transporters—Molecular Identification and Functional Role

The solute carrier family 41 (SLC41) encompasses three members A1, A2, and A3. Based on their distant homology to the bacterial Mg²⁺ channel MgtE, all have been linked to Mg²⁺ transport. There is only very limited knowledge on the molecular biology and exact functions of SLC41A2 and SLC41A3. SLC41A1 is ubiquitously expressed and data on its functional and molecular properties, regulation, complex-forming ability, and spectrum of binding partners are available. SLC41A1 was recently identified as being the Na⁺/Mg²⁺ exchanger (NME)-a predominant Mg²⁺ efflux system. Mg²⁺-dependent and hormonal regulation of NME activity is now known to depend on the intracellular N terminus of SLC41A1 that is involved in Mg²⁺ sensing and contains phosphorylation sites for protein kinase (PK) A and PKC. Data showing a link between SLC41A1 and human disorders such as Parkinson's disease, nephronophthisis (induced by the null mutation c.698G>T in renal SLC41A1), and preeclampsia make the protein a candidate therapeutic target.