title: Jen1p: a high affinity selenite transporter in yeast.
abstract: 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.
authors.affiliation: Department of Biological Sciences, Oakland University, Rochester, MI 48309, USA.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: McDermott
authors.forename: Barry P
authors.initials: BP
authors.lastname: Rosen
authors.forename: Zijuan
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000595:Amino Acid Sequence; D018053:Arsenites / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D005561:Formates / Q000494:pharmacology; D007700:Kinetics; D007773:Lactates / Q000378:metabolism / Q000493:pharmacokinetics; D008628:Mercury / Q000494:pharmacology; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D027501:Monocarboxylic Acid Transporters / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009550:Nigericin / Q000494:pharmacology; D019289:Pyruvic Acid / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D018038:Sodium Selenite / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D027981:Symporters / Q000235:genetics / Q000378:metabolism*
chemical_list: D018053:Arsenites; D005561:Formates; C118697:JEN1 protein, S cerevisiae; D007773:Lactates; D027501:Monocarboxylic Acid Transporters; D029701:Saccharomyces cerevisiae Proteins; D027981:Symporters; C030544:formic acid; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D019289:Pyruvic Acid; D008628:Mercury; D018038:Sodium Selenite; C015001:arsenite; D009550:Nigericin