Differential regulation of magnesium transporters Slc41, Cnnm and Trpm6-7 in the kidney of salmonids may represent evolutionary adaptations to high salinity environments.

Magnesium is important for enzymatic reactions and physiological functions, and its intracellular concentration is tightly regulated. Atlantic salmon has the ability to handle large changes in environmental Mg(2+) concentration when migrating between freshwater and seawater habitats, making it a relevant model to investigate Mg(2+) homeostasis. Parr-smolt transformation (PST) is a life history transition which prepares the freshwater juvenile for the marine environment. The kidney is one of the key organs involved in handling higher salt load in teleosts. Though several key Mg(2+) transport families (SLC41, CNNM and TRPM6-7) have recently been identified in mammals and a few fishes, the molecular bases of Mg(2+) homeostasis in salmon are not known. We found that all three families are represented in the salmon genome and exhibit a clear conservation of key functional domains and residues. Present study indicates a selective retention of paralogous Mg(2+) transporters from the fourth whole genome duplication round (Ss4R) and a differential regulation of these genes, which suggests neo- and/or sub-functionalization events. slc41a1-1, cnnm4a1, -4a2 and trpm7-2 are the main upregulated genes in the kidney during PST and remain high or further increase after exposure to seawater (33 ppt). By contrast, slc41a1-2, -3a, cnnm3-1, and cnnm3-2 are only upregulated after seawater exposure. In addition, slc41a1-1, -2, and trpm7-2 respond when exposed to brackish water (12 ppt), while cnnm3-1 and cnnm3-2 do not, indicating the existence of a lower salinity threshold response for these members. Finally, the response of slc41a1-1, -2 and trpm7-2 in salmon was significantly reduced or completely abolished when exposed to Mg(2+)-reduced brackish water, while others were not, suggesting they might be specifically regulated by Mg(2+). Our results are consistent with previous findings on other euryhaline teleosts and chondrichthyan species, suggesting the existence of common adaptive strategies to thrive in high salinity environments. Concomitantly, salmonid-specific innovations, such as differential regulation and recruitment of family members not previously shown to be regulated in the kidney (Cnnm1 and Cnnm4) of other vertebrates might point to adaptions associated with their very plastic anadromous life cycle.