Functional characterization of NIPA2, a selective Mg2+ transporter
Autor: | Angela Goytain, Gary A. Quamme, Rochelle M. Hines |
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Rok vydání: | 2008 |
Předmět: |
Male
Physiology Xenopus Molecular Sequence Data Cell Protein Array Analysis Biology Mice Downregulation and upregulation Angelman syndrome medicine Animals Magnesium Amino Acid Sequence Kidney Tubules Distal Cation Transport Proteins Peptide sequence Phylogeny Regulation of gene expression Microarray analysis techniques Gene Expression Profiling Biological Transport Transporter Cell Biology medicine.disease Molecular biology Gene expression profiling medicine.anatomical_structure Gene Expression Regulation Oocytes |
Zdroj: | American Journal of Physiology-Cell Physiology. 295:C944-C953 |
ISSN: | 1522-1563 0363-6143 |
DOI: | 10.1152/ajpcell.00091.2008 |
Popis: | 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 Mg2+ uptake with two-electrode voltage-clamp and fluorescence studies. Mg2+ transport was electrogenic, voltage dependent, and saturable, demonstrating a Michaelis affinity constant of 0.31 mM. Unlike other reported Mg2+ transporters, NIPA2 was very selective for the Mg2+ 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. |
Databáze: | OpenAIRE |
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