title: Functional characterization of NIPA2, a selective Mg2+ transporter.
abstract: We used microarray analysis to identify renal cell transcripts that were upregulated with low magnesium. One transcript, identified as NIPA2 (nonimprinted in Prader-Willi/Angelman syndrome) subtype 2, was increased over twofold relative to cells cultured in normal magnesium. The deduced sequence comprises 129 amino acids with 8 predicted transmembrane regions. As the secondary structure of NIPA2 conformed to a membrane transport protein, we expressed it in Xenopus oocytes and determined that it mediated Mg(2+) uptake with two-electrode voltage-clamp and fluorescence studies. Mg(2+) transport was electrogenic, voltage dependent, and saturable, demonstrating a Michaelis affinity constant of 0.31 mM. Unlike other reported Mg(2+) transporters, NIPA2 was very selective for the Mg(2+) cation. NIPA2 mRNA is found in many tissues but particularly abundant in renal cells. With the use of immunofluorescence, it was shown that NIPA2 protein was normally localized to the early endosomes and plasma membrane and was recruited to the plasma membrane in response to low extracellular magnesium. We conclude that NIPA2 plays a role in magnesium metabolism and regulation of renal magnesium conservation.
authors.affiliation: Department of Medicine, Vancouver Hospital, Koerner Pavilion, 2211 Wesbrook Mall, Vancouver, British Columbia, Canada V6T 1Z37.
authors.forename: Angela
authors.initials: A
authors.lastname: Goytain
authors.forename: Rochelle M
authors.initials: RM
authors.lastname: Hines
authors.forename: Gary A
authors.initials: GA
authors.lastname: Quamme
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007686:Kidney Tubules, Distal / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism; D010802:Phylogeny; D040081:Protein Array Analysis; D014981:Xenopus
chemical_list: D027682:Cation Transport Proteins; C533100:NIPA2 protein, mouse; D008274:Magnesium