A Physical Interaction between the Dopamine Transporter and DJ-1 Facilitates Increased Dopamine Reuptake
Identifieur interne : 000851 ( Main/Exploration ); précédent : 000850; suivant : 000852A Physical Interaction between the Dopamine Transporter and DJ-1 Facilitates Increased Dopamine Reuptake
Auteurs : Beryl Luk [Canada] ; Mohinuddin Mohammed [Canada] ; Fang Liu [Canada] ; Frank J. S. Lee [Canada]Source :
- PLoS ONE [ 1932-6203 ] ; 2015.
English descriptors
- KwdEn :
- Cell Membrane (metabolism), Dopamine (genetics), Dopamine (metabolism), Dopamine Plasma Membrane Transport Proteins (genetics), Dopamine Plasma Membrane Transport Proteins (metabolism), Dopaminergic Neurons (metabolism), Gene Expression Regulation, HEK293 Cells, Humans, Immunoprecipitation, Intracellular Signaling Peptides and Proteins (genetics), Intracellular Signaling Peptides and Proteins (metabolism), Mutation, Oncogene Proteins (genetics), Oncogene Proteins (metabolism), Parkinson Disease (genetics), Parkinson Disease (metabolism), Parkinson Disease (pathology), Protein Binding, Protein Deglycase DJ-1.
- MESH :
- chemical , genetics : Dopamine, Dopamine Plasma Membrane Transport Proteins, Intracellular Signaling Peptides and Proteins, Oncogene Proteins.
- genetics : Parkinson Disease.
- metabolism : Cell Membrane, Dopamine, Dopamine Plasma Membrane Transport Proteins, Dopaminergic Neurons, Intracellular Signaling Peptides and Proteins, Oncogene Proteins, Parkinson Disease.
- pathology : Parkinson Disease.
- Gene Expression Regulation, HEK293 Cells, Humans, Immunoprecipitation, Mutation, Protein Binding, Protein Deglycase DJ-1.
Abstract
The regulation of the dopamine transporter (DAT) impacts extracellular dopamine levels after release from dopaminergic neurons. Furthermore, a variety of protein partners have been identified that can interact with and modulate DAT function. In this study we show that DJ-1 can potentially modulate DAT function. Co-expression of DAT and DJ-1 in HEK-293T cells leads to an increase in [3H] dopamine uptake that does not appear to be mediated by increased total DAT expression but rather through an increase in DAT cell surface localization. In addition, through a series of GST affinity purifications and co-immunoprecipitations, we provide evidence that the DAT can be found in a complex with DJ-1, which involve distinct regions within both DAT and DJ-1. Using
Url:
DOI: 10.1371/journal.pone.0136641
PubMed: 26305376
PubMed Central: 4549284
Affiliations:
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Lee</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26305376</idno><idno type="pmc">4549284</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4549284</idno><idno type="RBID">PMC:4549284</idno><idno type="doi">10.1371/journal.pone.0136641</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">000081</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000081</idno><idno type="wicri:Area/Pmc/Curation">000081</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000081</idno><idno type="wicri:Area/Pmc/Checkpoint">000365</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000365</idno><idno type="wicri:source">PubMed</idno><idno type="wicri:Area/PubMed/Corpus">000438</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000438</idno><idno type="wicri:Area/PubMed/Curation">000438</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000438</idno><idno type="wicri:Area/PubMed/Checkpoint">000438</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000438</idno><idno type="wicri:Area/Ncbi/Merge">001C90</idno><idno type="wicri:Area/Ncbi/Curation">001C90</idno><idno type="wicri:Area/Ncbi/Checkpoint">001C90</idno><idno type="wicri:Area/Main/Merge">000852</idno><idno type="wicri:Area/Main/Curation">000851</idno><idno type="wicri:Area/Main/Exploration">000851</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">A Physical Interaction between the Dopamine Transporter and DJ-1 Facilitates Increased Dopamine Reuptake</title><author><name sortKey="Luk, Beryl" sort="Luk, Beryl" uniqKey="Luk B" first="Beryl" last="Luk">Beryl Luk</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation></author><author><name sortKey="Mohammed, Mohinuddin" sort="Mohammed, Mohinuddin" uniqKey="Mohammed M" first="Mohinuddin" last="Mohammed">Mohinuddin Mohammed</name><affiliation wicri:level="4"><nlm:aff id="aff002"><addr-line>Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Liu, Fang" sort="Liu, Fang" uniqKey="Liu F" first="Fang" last="Liu">Fang Liu</name><affiliation wicri:level="4"><nlm:aff id="aff002"><addr-line>Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Lee, Frank J S" sort="Lee, Frank J S" uniqKey="Lee F" first="Frank J. S." last="Lee">Frank J. S. Lee</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Cell Membrane (metabolism)</term><term>Dopamine (genetics)</term><term>Dopamine (metabolism)</term><term>Dopamine Plasma Membrane Transport Proteins (genetics)</term><term>Dopamine Plasma Membrane Transport Proteins (metabolism)</term><term>Dopaminergic Neurons (metabolism)</term><term>Gene Expression Regulation</term><term>HEK293 Cells</term><term>Humans</term><term>Immunoprecipitation</term><term>Intracellular Signaling Peptides and Proteins (genetics)</term><term>Intracellular Signaling Peptides and Proteins (metabolism)</term><term>Mutation</term><term>Oncogene Proteins (genetics)</term><term>Oncogene Proteins (metabolism)</term><term>Parkinson Disease (genetics)</term><term>Parkinson Disease (metabolism)</term><term>Parkinson Disease (pathology)</term><term>Protein Binding</term><term>Protein Deglycase DJ-1</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Dopamine</term><term>Dopamine Plasma Membrane Transport Proteins</term><term>Intracellular Signaling Peptides and Proteins</term><term>Oncogene Proteins</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Cell Membrane</term><term>Dopamine</term><term>Dopamine Plasma Membrane Transport Proteins</term><term>Dopaminergic Neurons</term><term>Intracellular Signaling Peptides and Proteins</term><term>Oncogene Proteins</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Gene Expression Regulation</term><term>HEK293 Cells</term><term>Humans</term><term>Immunoprecipitation</term><term>Mutation</term><term>Protein Binding</term><term>Protein Deglycase DJ-1</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The regulation of the dopamine transporter (DAT) impacts extracellular dopamine levels after release from dopaminergic neurons. Furthermore, a variety of protein partners have been identified that can interact with and modulate DAT function. In this study we show that DJ-1 can potentially modulate DAT function. Co-expression of DAT and DJ-1 in HEK-293T cells leads to an increase in [<sup>3</sup>H] dopamine uptake that does not appear to be mediated by increased total DAT expression but rather through an increase in DAT cell surface localization. In addition, through a series of GST affinity purifications and co-immunoprecipitations, we provide evidence that the DAT can be found in a complex with DJ-1, which involve distinct regions within both DAT and DJ-1. Using <italic>in vitro</italic> binding experiments we also show that this complex can be formed in part by a direct interaction between DAT and DJ-1. Co-expression of a mini-gene that can disrupt the DAT/DJ-1 complex appears to block the increase in [<sup>3</sup>H] dopamine uptake by DJ-1. Mutations in DJ-1 have been linked to familial forms of Parkinson’s disease, yet the normal physiological function of DJ-1 remains unclear. Our study suggests that DJ-1 may also play a role in regulating dopamine levels by modifying DAT activity.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Hersch, Sm" uniqKey="Hersch S">SM Hersch</name></author><author><name sortKey="Yi, H" uniqKey="Yi H">H Yi</name></author><author><name sortKey="Heilman, Cj" uniqKey="Heilman C">CJ Heilman</name></author><author><name sortKey="Edwards, Rh" uniqKey="Edwards R">RH Edwards</name></author><author><name sortKey="Levey, Ai" uniqKey="Levey A">AI Levey</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Descarries, L" uniqKey="Descarries L">L Descarries</name></author><author><name sortKey="Watkins, Kc" uniqKey="Watkins K">KC Watkins</name></author><author><name sortKey="Garcia, S" uniqKey="Garcia S">S Garcia</name></author><author><name sortKey="Bosler, O" uniqKey="Bosler O">O Bosler</name></author><author><name sortKey="Doucet, G" uniqKey="Doucet G">G 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Zhang</name></author><author><name sortKey="Vukusic, B" uniqKey="Vukusic B">B Vukusic</name></author><author><name sortKey="Lee, Fj" uniqKey="Lee F">FJ Lee</name></author><author><name sortKey="Liu, F" uniqKey="Liu F">F Liu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Graham, Dg" uniqKey="Graham D">DG Graham</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Olanow, Cw" uniqKey="Olanow C">CW Olanow</name></author><author><name sortKey="Arendash, Gw" uniqKey="Arendash G">GW Arendash</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Napolitano, A" uniqKey="Napolitano A">A Napolitano</name></author><author><name sortKey="Crescenzi, O" uniqKey="Crescenzi O">O Crescenzi</name></author><author><name sortKey="Pezzella, A" uniqKey="Pezzella A">A Pezzella</name></author><author><name sortKey="Prota, G" uniqKey="Prota G">G Prota</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, L" uniqKey="Chen L">L Chen</name></author><author><name sortKey="Ding, Y" uniqKey="Ding Y">Y Ding</name></author><author><name sortKey="Cagniard, B" uniqKey="Cagniard B">B Cagniard</name></author><author><name sortKey="Van Laar, Ad" uniqKey="Van Laar A">AD Van Laar</name></author><author><name sortKey="Mortimer, A" uniqKey="Mortimer A">A Mortimer</name></author><author><name sortKey="Chi, W" uniqKey="Chi W">W Chi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Caudle, Wm" uniqKey="Caudle W">WM Caudle</name></author><author><name sortKey="Richardson, Jr" uniqKey="Richardson J">JR Richardson</name></author><author><name sortKey="Wang, Mz" uniqKey="Wang M">MZ Wang</name></author><author><name sortKey="Taylor, Tn" uniqKey="Taylor T">TN Taylor</name></author><author><name sortKey="Guillot, Ts" uniqKey="Guillot T">TS Guillot</name></author><author><name sortKey="Mccormack, Al" uniqKey="Mccormack A">AL McCormack</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Canada</li></country><region><li>Ontario</li></region><settlement><li>Toronto</li></settlement><orgName><li>Université de Toronto</li></orgName></list><tree><country name="Canada"><noRegion><name sortKey="Luk, Beryl" sort="Luk, Beryl" uniqKey="Luk B" first="Beryl" last="Luk">Beryl Luk</name></noRegion><name sortKey="Lee, Frank J S" sort="Lee, Frank J S" uniqKey="Lee F" first="Frank J. S." last="Lee">Frank J. S. Lee</name><name sortKey="Liu, Fang" sort="Liu, Fang" uniqKey="Liu F" first="Fang" last="Liu">Fang Liu</name><name sortKey="Mohammed, Mohinuddin" sort="Mohammed, Mohinuddin" uniqKey="Mohammed M" first="Mohinuddin" last="Mohammed">Mohinuddin Mohammed</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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