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Article ; Online: SLC41A1 Mg(2+) transport is regulated via Mg(2+)-dependent endosomal recycling through its N-terminal cytoplasmic domain.

Mandt, Tyler / Song, Yumei / Scharenberg, Andrew M / Sahni, Jaya

The Biochemical journal

2011  Volume 439, Issue 1, Page(s) 129–139

Abstract: ... when the Mg(2+) transporting pore is intact, and require an N-terminal cytoplasmic domain for Mg(2+)-dependent ... function is regulated primarily through an endosomal recycling mechanism involving the SLC41A1 N-terminal ... organisms, and are highly conserved, little is known about the regulation of their Mg(2+) transport function ...

Abstract SLC41A1 (solute carrier family 41, member A1) is a recently described vertebrate member of the MgtE family of Mg(2+) transporters. Although MgtE transporters are found in both prokaryotic and eukaryotic organisms, and are highly conserved, little is known about the regulation of their Mg(2+) transport function. In the present study, we have shown that endogenous SLC41A1 transporter expression is post-transcriptionally regulated by extracellular Mg(2+) in TRPM7 (transient receptor potential cation channel, subfamily M, member 7)-deficient cells, suggesting that SLC41A1 transporters underlie a novel plasma membrane Mg(2+) transport function. Consistent with this conclusion, structure-function analyses of heterologous SLC41A1 transporter expression demonstrate that SLC41A1 transporters exhibit the same plasma membrane orientation as homologous bacterial MgtE proteins, are capable of complementing growth of TRPM7-deficient cells only when the Mg(2+) transporting pore is intact, and require an N-terminal cytoplasmic domain for Mg(2+)-dependent regulation of lysosomal degradation and surface expression. Taken together, our results indicate that SLC41A1 proteins are a central component of vertebrate Mg(2+) transport systems, and that their Mg(2+) transport function is regulated primarily through an endosomal recycling mechanism involving the SLC41A1 N-terminal cytoplasmic domain.
MeSH term(s) Animals ; Blotting, Western ; Cation Transport Proteins/chemistry ; Cation Transport Proteins/genetics ; Cation Transport Proteins/metabolism ; Cell Line ; Chickens ; Electrophoresis, Polyacrylamide Gel ; Endosomes/metabolism ; Humans ; Magnesium/metabolism ; Polymerase Chain Reaction ; Protein Structure, Tertiary/genetics ; Protein Structure, Tertiary/physiology ; Protein Transport
Chemical Substances Cation Transport Proteins ; SLC41A1 protein, human ; Magnesium (I38ZP9992A)
Language English
Publishing date 2011-10-01
Publishing country England
Document type Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID 2969-5
ISSN 1470-8728 ; 0006-2936 ; 0306-3275 ; 0264-6021
ISSN (online) 1470-8728
ISSN 0006-2936 ; 0306-3275 ; 0264-6021
DOI 10.1042/BJ20110807
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