Jen1p: a high affinity selenite transporter in yeast

Selenium is a micronutrient in most eukaryotes, including humans, which is well known for having an extremely thin border between beneficial and toxic concentrations. Soluble tetravalent selenite is the predominant environmental form and also the form that is applied in the treatment of human diseas...

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Veröffentlicht in:Molecular biology of the cell 2010-11, Vol.21 (22), p.3934-3941
Hauptverfasser: McDermott, Joseph R, Rosen, Barry P, Liu, Zijuan
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Rosen, Barry P
Liu, Zijuan
description Selenium is a micronutrient in most eukaryotes, including humans, which is well known for having an extremely thin border between beneficial and toxic concentrations. Soluble tetravalent selenite is the predominant environmental form and also the form that is applied in the treatment of human diseases. To acquire this nutrient from low environmental concentrations as well as to avoid toxicity, a well-controlled transport system is required. Here we report that Jen1p, a proton-coupled monocarboxylate transporter in S. cerevisiae, catalyzes high-affinity uptake of selenite. Disruption of JEN1 resulted in selenite resistance, and overexpression resulted in selenite hypersensitivity. Transport assay showed that overexpression of Jen1p enables selenite accumulation in yeast compared with a JEN1 knock out strain, indicating the Jen1p transporter facilitates selenite accumulation inside cells. Selenite uptake by Jen1p had a Km of 0.91 mM, which is comparable to the Km for lactate. Jen1p transported selenite in a proton-dependent manner which resembles the transport mechanism for lactate. In addition, selenite and lactate can inhibit the transport of each other competitively. Therefore, we postulate selenite is a molecular mimic of monocarboxylates which allows selenite to be transported by Jen1p.
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Soluble tetravalent selenite is the predominant environmental form and also the form that is applied in the treatment of human diseases. To acquire this nutrient from low environmental concentrations as well as to avoid toxicity, a well-controlled transport system is required. Here we report that Jen1p, a proton-coupled monocarboxylate transporter in S. cerevisiae, catalyzes high-affinity uptake of selenite. Disruption of JEN1 resulted in selenite resistance, and overexpression resulted in selenite hypersensitivity. Transport assay showed that overexpression of Jen1p enables selenite accumulation in yeast compared with a JEN1 knock out strain, indicating the Jen1p transporter facilitates selenite accumulation inside cells. Selenite uptake by Jen1p had a Km of 0.91 mM, which is comparable to the Km for lactate. Jen1p transported selenite in a proton-dependent manner which resembles the transport mechanism for lactate. 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subjects Amino Acid Sequence
Arsenites - pharmacology
Biological Transport - drug effects
Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone - pharmacology
Cell Membrane - metabolism
Formates - pharmacology
Kinetics
Lactates - metabolism
Lactates - pharmacokinetics
Mercury - pharmacology
Microscopy, Fluorescence
Molecular Sequence Data
Monocarboxylic Acid Transporters - genetics
Monocarboxylic Acid Transporters - metabolism
Mutation
Nigericin - pharmacology
Pyruvic Acid - pharmacology
Saccharomyces cerevisiae - drug effects
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae - metabolism
Saccharomyces cerevisiae Proteins - genetics
Saccharomyces cerevisiae Proteins - metabolism
Sodium Selenite - metabolism
Sodium Selenite - pharmacokinetics
Sodium Selenite - pharmacology
Symporters - genetics
Symporters - metabolism
title Jen1p: a high affinity selenite transporter in yeast
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