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 |
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creator | McDermott, Joseph R 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. |
doi_str_mv | 10.1091/mbc.e10-06-0513 |
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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. 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.</description><identifier>ISSN: 1059-1524</identifier><identifier>EISSN: 1939-4586</identifier><identifier>DOI: 10.1091/mbc.e10-06-0513</identifier><identifier>PMID: 20861301</identifier><language>eng</language><publisher>United States: The American Society for Cell Biology</publisher><subject>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</subject><ispartof>Molecular biology of the cell, 2010-11, Vol.21 (22), p.3934-3941</ispartof><rights>2010 by The American Society for Cell Biology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c490t-a99791dcc4ee4c9cd31c5fc79daaf2acb2b643a7c7c92349007f1bf897e9a4cd3</citedby><cites>FETCH-LOGICAL-c490t-a99791dcc4ee4c9cd31c5fc79daaf2acb2b643a7c7c92349007f1bf897e9a4cd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2982120/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2982120/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20861301$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Glick, Benjamin S.</contributor><creatorcontrib>McDermott, Joseph R</creatorcontrib><creatorcontrib>Rosen, Barry P</creatorcontrib><creatorcontrib>Liu, Zijuan</creatorcontrib><title>Jen1p: a high affinity selenite transporter in yeast</title><title>Molecular biology of the cell</title><addtitle>Mol Biol Cell</addtitle><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.</description><subject>Amino Acid Sequence</subject><subject>Arsenites - pharmacology</subject><subject>Biological Transport - drug effects</subject><subject>Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone - pharmacology</subject><subject>Cell Membrane - metabolism</subject><subject>Formates - pharmacology</subject><subject>Kinetics</subject><subject>Lactates - metabolism</subject><subject>Lactates - pharmacokinetics</subject><subject>Mercury - pharmacology</subject><subject>Microscopy, Fluorescence</subject><subject>Molecular Sequence Data</subject><subject>Monocarboxylic Acid Transporters - genetics</subject><subject>Monocarboxylic Acid Transporters - metabolism</subject><subject>Mutation</subject><subject>Nigericin - pharmacology</subject><subject>Pyruvic Acid - pharmacology</subject><subject>Saccharomyces cerevisiae - drug effects</subject><subject>Saccharomyces cerevisiae - genetics</subject><subject>Saccharomyces cerevisiae - metabolism</subject><subject>Saccharomyces cerevisiae Proteins - genetics</subject><subject>Saccharomyces cerevisiae Proteins - metabolism</subject><subject>Sodium Selenite - metabolism</subject><subject>Sodium Selenite - pharmacokinetics</subject><subject>Sodium Selenite - pharmacology</subject><subject>Symporters - genetics</subject><subject>Symporters - metabolism</subject><issn>1059-1524</issn><issn>1939-4586</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkM1LAzEQxYMotlbP3mRvnrad2WQ_4kGQ4icFL3oO2eykXdmPmmyF_vemVIueZmDee_P4MXaJMEWQOGtLMyWEGLIYUuRHbIySy1ikRXYcdkhljGkiRuzM-w8AFCLLT9kogSJDDjhm4oU6XN9EOlrVy1Wkra27ethGnhoKC0WD051f924gF9VdtCXth3N2YnXj6eJnTtj7w_3b_ClevD4-z-8WsREShlhLmUusjBFEwkhTcTSpNbmstLaJNmVSZoLr3ORGJjxYILdY2kLmJLUI8gm73eeuN2VLlaEutGnU2tWtdlvV61r9v3T1Si37L5XIIsEEQsD1T4DrPzfkB9XW3lDT6I76jVcSCxAgOAblbK80rvfekT18QVA71CqgVgG1gkztUAfH1d9yB_0vW_4NBtR7yw</recordid><startdate>20101115</startdate><enddate>20101115</enddate><creator>McDermott, Joseph R</creator><creator>Rosen, Barry P</creator><creator>Liu, Zijuan</creator><general>The American Society for Cell Biology</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>M7N</scope><scope>5PM</scope></search><sort><creationdate>20101115</creationdate><title>Jen1p: a high affinity selenite transporter in yeast</title><author>McDermott, Joseph R ; Rosen, Barry P ; Liu, Zijuan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c490t-a99791dcc4ee4c9cd31c5fc79daaf2acb2b643a7c7c92349007f1bf897e9a4cd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Amino Acid Sequence</topic><topic>Arsenites - pharmacology</topic><topic>Biological Transport - drug effects</topic><topic>Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone - pharmacology</topic><topic>Cell Membrane - metabolism</topic><topic>Formates - pharmacology</topic><topic>Kinetics</topic><topic>Lactates - metabolism</topic><topic>Lactates - pharmacokinetics</topic><topic>Mercury - pharmacology</topic><topic>Microscopy, Fluorescence</topic><topic>Molecular Sequence Data</topic><topic>Monocarboxylic Acid Transporters - genetics</topic><topic>Monocarboxylic Acid Transporters - metabolism</topic><topic>Mutation</topic><topic>Nigericin - pharmacology</topic><topic>Pyruvic Acid - pharmacology</topic><topic>Saccharomyces cerevisiae - drug effects</topic><topic>Saccharomyces cerevisiae - genetics</topic><topic>Saccharomyces cerevisiae - metabolism</topic><topic>Saccharomyces cerevisiae Proteins - genetics</topic><topic>Saccharomyces cerevisiae Proteins - metabolism</topic><topic>Sodium Selenite - metabolism</topic><topic>Sodium Selenite - pharmacokinetics</topic><topic>Sodium Selenite - pharmacology</topic><topic>Symporters - genetics</topic><topic>Symporters - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>McDermott, Joseph R</creatorcontrib><creatorcontrib>Rosen, Barry P</creatorcontrib><creatorcontrib>Liu, Zijuan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular biology of the cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>McDermott, Joseph R</au><au>Rosen, Barry P</au><au>Liu, Zijuan</au><au>Glick, Benjamin S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Jen1p: a high affinity selenite transporter in yeast</atitle><jtitle>Molecular biology of the cell</jtitle><addtitle>Mol Biol Cell</addtitle><date>2010-11-15</date><risdate>2010</risdate><volume>21</volume><issue>22</issue><spage>3934</spage><epage>3941</epage><pages>3934-3941</pages><issn>1059-1524</issn><eissn>1939-4586</eissn><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.</abstract><cop>United States</cop><pub>The American Society for Cell Biology</pub><pmid>20861301</pmid><doi>10.1091/mbc.e10-06-0513</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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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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