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2016 ; 291
(38
): 20163-72
Nephropedia Template TP
Valinsky WC
; Jolly A
; Miquel P
; Touyz RM
; Shrier A
J Biol Chem
2016[Sep]; 291
(38
): 20163-72
PMID27466368
show ga
Transient receptor potential melastatin 7 (TRPM7) is a ubiquitously expressed
Mg(2+)-permeable ion channel fused to a C-terminal ?-kinase domain. Recently,
aldosterone was shown to increase intracellular Mg(2+) levels and alter
inflammatory signaling in TRPM7-expressing HEK293 cells. This study was
undertaken to assess whether these effects were related to an
aldosterone-mediated increase of TRPM7 current and/or plasma membrane
localization. Using HEK293 cells stably expressing WT-TRPM7, we found that 18-h
application of aldosterone significantly increased TRPM7 current and TRPM7 plasma
membrane protein expression by 48% and 34%, respectively. The
aldosterone-mediated increase of TRPM7 current was inhibited by eplerenone, a
mineralocorticoid receptor (MR) blocker, and GSK-650394, an inhibitor of the
serum- and glucocorticoid-regulated kinase 1 (SGK1). SGK1 blockade also prevented
the aldosterone-induced increase of TRPM7 plasma membrane protein. It was further
determined that K1648R-TRPM7, the phosphotransferase-inactive TRPM7 mutant, was
unresponsive to aldosterone. Therefore, chronic aldosterone treatment increases
the plasma membrane expression of TRPM7, which is associated with an increase of
TRPM7 current. This process occurs via an MR-dependent, genomic signaling cascade
involving SGK1 and a functioning TRPM7 ?-kinase domain. We suggest that this
mechanism may be of general relevance when interpreting the effects of
aldosterone because the MR receptor is found in multiple tissues, and TRPM7 and
SGK1 are ubiquitously expressed.
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