α-Synuclein Membrane Association Is Regulated by the Rab3a Recycling Machinery and Presynaptic Activity*♦
Identifieur interne : 001367 ( Ncbi/Merge ); précédent : 001366; suivant : 001368α-Synuclein Membrane Association Is Regulated by the Rab3a Recycling Machinery and Presynaptic Activity*♦
Auteurs : Robert H. C. Chen ; Sabine Wislet-Gendebien ; Filsy Samuel ; Naomi P. Visanji ; Gang Zhang ; Diana Marsilio ; Tammy Langman ; Paul E. Fraser ; Anurag Tandon [Canada]Source :
- The Journal of Biological Chemistry [ 0021-9258 ] ; 2013.
English descriptors
- KwdEn :
- Animals, Brain (metabolism), Cell Line, Tumor, Cell Membrane (metabolism), Cytosol (metabolism), Epitopes (chemistry), Glycerol (chemistry), Guanosine Triphosphate (metabolism), HSP90 Heat-Shock Proteins (metabolism), Humans, Mice, Mice, Transgenic, Models, Biological, Neurodegenerative Diseases (metabolism), Neurons (metabolism), Subcellular Fractions (metabolism), Synapses (metabolism), Synaptosomes (metabolism), alpha-Synuclein (chemistry), alpha-Synuclein (metabolism), rab3A GTP-Binding Protein (metabolism).
- MESH :
- chemical , chemistry : Epitopes, Glycerol, alpha-Synuclein.
- metabolism : Brain, Cell Membrane, Cytosol, Guanosine Triphosphate, HSP90 Heat-Shock Proteins, Neurodegenerative Diseases, Neurons, Subcellular Fractions, Synapses, Synaptosomes, alpha-Synuclein, rab3A GTP-Binding Protein.
- Animals, Cell Line, Tumor, Humans, Mice, Mice, Transgenic, Models, Biological.
Abstract
Url:
DOI: 10.1074/jbc.M112.439497
PubMed: 23344955
PubMed Central: 3597785
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PMC:3597785Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">α-Synuclein Membrane Association Is Regulated by the Rab3a Recycling Machinery and Presynaptic Activity<xref ref-type="fn" rid="FN1">*</xref><xref ref-type="fn" rid="FN2"><sup>♦</sup></xref></title><author><name sortKey="Chen, Robert H C" sort="Chen, Robert H C" uniqKey="Chen R" first="Robert H. C." last="Chen">Robert H. C. Chen</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Wislet Gendebien, Sabine" sort="Wislet Gendebien, Sabine" uniqKey="Wislet Gendebien S" first="Sabine" last="Wislet-Gendebien">Sabine Wislet-Gendebien</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Samuel, Filsy" sort="Samuel, Filsy" uniqKey="Samuel F" first="Filsy" last="Samuel">Filsy Samuel</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Visanji, Naomi P" sort="Visanji, Naomi P" uniqKey="Visanji N" first="Naomi P." last="Visanji">Naomi P. Visanji</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Zhang, Gang" sort="Zhang, Gang" uniqKey="Zhang G" first="Gang" last="Zhang">Gang Zhang</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Marsilio, Diana" sort="Marsilio, Diana" uniqKey="Marsilio D" first="Diana" last="Marsilio">Diana Marsilio</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Langman, Tammy" sort="Langman, Tammy" uniqKey="Langman T" first="Tammy" last="Langman">Tammy Langman</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Fraser, Paul E" sort="Fraser, Paul E" uniqKey="Fraser P" first="Paul E." last="Fraser">Paul E. Fraser</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Tandon, Anurag" sort="Tandon, Anurag" uniqKey="Tandon A" first="Anurag" last="Tandon">Anurag Tandon</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation wicri:level="4"><nlm:aff id="aff3">Medicine, University of Toronto, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Medicine, 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></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">23344955</idno><idno type="pmc">3597785</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3597785</idno><idno type="RBID">PMC:3597785</idno><idno type="doi">10.1074/jbc.M112.439497</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">000571</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000571</idno><idno type="wicri:Area/Pmc/Curation">000571</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000571</idno><idno type="wicri:Area/Pmc/Checkpoint">000552</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000552</idno><idno type="wicri:source">PubMed</idno><idno type="wicri:Area/PubMed/Corpus">000946</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000946</idno><idno type="wicri:Area/PubMed/Curation">000946</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000946</idno><idno type="wicri:Area/PubMed/Checkpoint">000946</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000946</idno><idno type="wicri:Area/Ncbi/Merge">001367</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">α-Synuclein Membrane Association Is Regulated by the Rab3a Recycling Machinery and Presynaptic Activity<xref ref-type="fn" rid="FN1">*</xref><xref ref-type="fn" rid="FN2"><sup>♦</sup></xref></title><author><name sortKey="Chen, Robert H C" sort="Chen, Robert H C" uniqKey="Chen R" first="Robert H. C." last="Chen">Robert H. C. Chen</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Wislet Gendebien, Sabine" sort="Wislet Gendebien, Sabine" uniqKey="Wislet Gendebien S" first="Sabine" last="Wislet-Gendebien">Sabine Wislet-Gendebien</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Samuel, Filsy" sort="Samuel, Filsy" uniqKey="Samuel F" first="Filsy" last="Samuel">Filsy Samuel</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Visanji, Naomi P" sort="Visanji, Naomi P" uniqKey="Visanji N" first="Naomi P." last="Visanji">Naomi P. Visanji</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Zhang, Gang" sort="Zhang, Gang" uniqKey="Zhang G" first="Gang" last="Zhang">Gang Zhang</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Marsilio, Diana" sort="Marsilio, Diana" uniqKey="Marsilio D" first="Diana" last="Marsilio">Diana Marsilio</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Langman, Tammy" sort="Langman, Tammy" uniqKey="Langman T" first="Tammy" last="Langman">Tammy Langman</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Fraser, Paul E" sort="Fraser, Paul E" uniqKey="Fraser P" first="Paul E." last="Fraser">Paul E. Fraser</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Tandon, Anurag" sort="Tandon, Anurag" uniqKey="Tandon A" first="Anurag" last="Tandon">Anurag Tandon</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation wicri:level="4"><nlm:aff id="aff3">Medicine, University of Toronto, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Medicine, 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></analytic><series><title level="j">The Journal of Biological Chemistry</title><idno type="ISSN">0021-9258</idno><idno type="eISSN">1083-351X</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Brain (metabolism)</term><term>Cell Line, Tumor</term><term>Cell Membrane (metabolism)</term><term>Cytosol (metabolism)</term><term>Epitopes (chemistry)</term><term>Glycerol (chemistry)</term><term>Guanosine Triphosphate (metabolism)</term><term>HSP90 Heat-Shock Proteins (metabolism)</term><term>Humans</term><term>Mice</term><term>Mice, Transgenic</term><term>Models, Biological</term><term>Neurodegenerative Diseases (metabolism)</term><term>Neurons (metabolism)</term><term>Subcellular Fractions (metabolism)</term><term>Synapses (metabolism)</term><term>Synaptosomes (metabolism)</term><term>alpha-Synuclein (chemistry)</term><term>alpha-Synuclein (metabolism)</term><term>rab3A GTP-Binding Protein (metabolism)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Epitopes</term><term>Glycerol</term><term>alpha-Synuclein</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Brain</term><term>Cell Membrane</term><term>Cytosol</term><term>Guanosine Triphosphate</term><term>HSP90 Heat-Shock Proteins</term><term>Neurodegenerative Diseases</term><term>Neurons</term><term>Subcellular Fractions</term><term>Synapses</term><term>Synaptosomes</term><term>alpha-Synuclein</term><term>rab3A GTP-Binding Protein</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Line, Tumor</term><term>Humans</term><term>Mice</term><term>Mice, Transgenic</term><term>Models, Biological</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><bold>Background:</bold> α-Synuclein is known to undergo exchange between membrane and cytosolic compartments.</p><p><bold>Results:</bold> α-Synuclein interacts with GTP-bound Rab3a on synaptic vesicles, and its dissociation is mediated by GDI/Hsp90.</p><p><bold>Conclusion:</bold> α-Synuclein's membrane association and dissociation cycle is linked to synaptic activity by the Rab3a recycling machinery.</p><p><bold>Significance:</bold> Significance: Impairments to α-synuclein interactions with vesicles and with the Rab3a recycling machinery may affect neurodegeneration.</p></div></front></TEI><double pmid="23344955"><pmc><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">α-Synuclein Membrane Association Is Regulated by the Rab3a Recycling Machinery and Presynaptic Activity<xref ref-type="fn" rid="FN1">*</xref><xref ref-type="fn" rid="FN2"><sup>♦</sup></xref></title><author><name sortKey="Chen, Robert H C" sort="Chen, Robert H C" uniqKey="Chen R" first="Robert H. C." last="Chen">Robert H. C. Chen</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Wislet Gendebien, Sabine" sort="Wislet Gendebien, Sabine" uniqKey="Wislet Gendebien S" first="Sabine" last="Wislet-Gendebien">Sabine Wislet-Gendebien</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Samuel, Filsy" sort="Samuel, Filsy" uniqKey="Samuel F" first="Filsy" last="Samuel">Filsy Samuel</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Visanji, Naomi P" sort="Visanji, Naomi P" uniqKey="Visanji N" first="Naomi P." last="Visanji">Naomi P. Visanji</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Zhang, Gang" sort="Zhang, Gang" uniqKey="Zhang G" first="Gang" last="Zhang">Gang Zhang</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Marsilio, Diana" sort="Marsilio, Diana" uniqKey="Marsilio D" first="Diana" last="Marsilio">Diana Marsilio</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Langman, Tammy" sort="Langman, Tammy" uniqKey="Langman T" first="Tammy" last="Langman">Tammy Langman</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Fraser, Paul E" sort="Fraser, Paul E" uniqKey="Fraser P" first="Paul E." last="Fraser">Paul E. Fraser</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Tandon, Anurag" sort="Tandon, Anurag" uniqKey="Tandon A" first="Anurag" last="Tandon">Anurag Tandon</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation wicri:level="4"><nlm:aff id="aff3">Medicine, University of Toronto, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Medicine, 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></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">23344955</idno><idno type="pmc">3597785</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3597785</idno><idno type="RBID">PMC:3597785</idno><idno type="doi">10.1074/jbc.M112.439497</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">000571</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000571</idno><idno type="wicri:Area/Pmc/Curation">000571</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000571</idno><idno type="wicri:Area/Pmc/Checkpoint">000552</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000552</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">α-Synuclein Membrane Association Is Regulated by the Rab3a Recycling Machinery and Presynaptic Activity<xref ref-type="fn" rid="FN1">*</xref><xref ref-type="fn" rid="FN2"><sup>♦</sup></xref></title><author><name sortKey="Chen, Robert H C" sort="Chen, Robert H C" uniqKey="Chen R" first="Robert H. C." last="Chen">Robert H. C. Chen</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Wislet Gendebien, Sabine" sort="Wislet Gendebien, Sabine" uniqKey="Wislet Gendebien S" first="Sabine" last="Wislet-Gendebien">Sabine Wislet-Gendebien</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Samuel, Filsy" sort="Samuel, Filsy" uniqKey="Samuel F" first="Filsy" last="Samuel">Filsy Samuel</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Visanji, Naomi P" sort="Visanji, Naomi P" uniqKey="Visanji N" first="Naomi P." last="Visanji">Naomi P. Visanji</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Zhang, Gang" sort="Zhang, Gang" uniqKey="Zhang G" first="Gang" last="Zhang">Gang Zhang</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Marsilio, Diana" sort="Marsilio, Diana" uniqKey="Marsilio D" first="Diana" last="Marsilio">Diana Marsilio</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Langman, Tammy" sort="Langman, Tammy" uniqKey="Langman T" first="Tammy" last="Langman">Tammy Langman</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Fraser, Paul E" sort="Fraser, Paul E" uniqKey="Fraser P" first="Paul E." last="Fraser">Paul E. Fraser</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Tandon, Anurag" sort="Tandon, Anurag" uniqKey="Tandon A" first="Anurag" last="Tandon">Anurag Tandon</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation wicri:level="4"><nlm:aff id="aff3">Medicine, University of Toronto, Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Medicine, 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></analytic><series><title level="j">The Journal of Biological Chemistry</title><idno type="ISSN">0021-9258</idno><idno type="eISSN">1083-351X</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><bold>Background:</bold> α-Synuclein is known to undergo exchange between membrane and cytosolic compartments.</p><p><bold>Results:</bold> α-Synuclein interacts with GTP-bound Rab3a on synaptic vesicles, and its dissociation is mediated by GDI/Hsp90.</p><p><bold>Conclusion:</bold> α-Synuclein's membrane association and dissociation cycle is linked to synaptic activity by the Rab3a recycling machinery.</p><p><bold>Significance:</bold> Significance: Impairments to α-synuclein interactions with vesicles and with the Rab3a recycling machinery may affect neurodegeneration.</p></div></front></TEI></pmc><pubmed><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">α-Synuclein membrane association is regulated by the Rab3a recycling machinery and presynaptic activity.</title><author><name sortKey="Chen, Robert H C" sort="Chen, Robert H C" uniqKey="Chen R" first="Robert H C" last="Chen">Robert H C. Chen</name><affiliation wicri:level="4"><nlm:affiliation>Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario M5S 3H2, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario M5S 3H2</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="Wislet Gendebien, Sabine" sort="Wislet Gendebien, Sabine" uniqKey="Wislet Gendebien S" first="Sabine" last="Wislet-Gendebien">Sabine Wislet-Gendebien</name></author><author><name sortKey="Samuel, Filsy" sort="Samuel, Filsy" uniqKey="Samuel F" first="Filsy" last="Samuel">Filsy Samuel</name></author><author><name sortKey="Visanji, Naomi P" sort="Visanji, Naomi P" uniqKey="Visanji N" first="Naomi P" last="Visanji">Naomi P. Visanji</name></author><author><name sortKey="Zhang, Gang" sort="Zhang, Gang" uniqKey="Zhang G" first="Gang" last="Zhang">Gang Zhang</name></author><author><name sortKey="Marsilio, Diana" sort="Marsilio, Diana" uniqKey="Marsilio D" first="Diana" last="Marsilio">Diana Marsilio</name></author><author><name sortKey="Langman, Tammy" sort="Langman, Tammy" uniqKey="Langman T" first="Tammy" last="Langman">Tammy Langman</name></author><author><name sortKey="Fraser, Paul E" sort="Fraser, Paul E" uniqKey="Fraser P" first="Paul E" last="Fraser">Paul E. Fraser</name></author><author><name sortKey="Tandon, Anurag" sort="Tandon, Anurag" uniqKey="Tandon A" first="Anurag" last="Tandon">Anurag Tandon</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2013">2013</date><idno type="RBID">pubmed:23344955</idno><idno type="pmid">23344955</idno><idno type="doi">10.1074/jbc.M112.439497</idno><idno type="wicri:Area/PubMed/Corpus">000946</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000946</idno><idno type="wicri:Area/PubMed/Curation">000946</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000946</idno><idno type="wicri:Area/PubMed/Checkpoint">000946</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000946</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">α-Synuclein membrane association is regulated by the Rab3a recycling machinery and presynaptic activity.</title><author><name sortKey="Chen, Robert H C" sort="Chen, Robert H C" uniqKey="Chen R" first="Robert H C" last="Chen">Robert H C. Chen</name><affiliation wicri:level="4"><nlm:affiliation>Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario M5S 3H2, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario M5S 3H2</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="Wislet Gendebien, Sabine" sort="Wislet Gendebien, Sabine" uniqKey="Wislet Gendebien S" first="Sabine" last="Wislet-Gendebien">Sabine Wislet-Gendebien</name></author><author><name sortKey="Samuel, Filsy" sort="Samuel, Filsy" uniqKey="Samuel F" first="Filsy" last="Samuel">Filsy Samuel</name></author><author><name sortKey="Visanji, Naomi P" sort="Visanji, Naomi P" uniqKey="Visanji N" first="Naomi P" last="Visanji">Naomi P. Visanji</name></author><author><name sortKey="Zhang, Gang" sort="Zhang, Gang" uniqKey="Zhang G" first="Gang" last="Zhang">Gang Zhang</name></author><author><name sortKey="Marsilio, Diana" sort="Marsilio, Diana" uniqKey="Marsilio D" first="Diana" last="Marsilio">Diana Marsilio</name></author><author><name sortKey="Langman, Tammy" sort="Langman, Tammy" uniqKey="Langman T" first="Tammy" last="Langman">Tammy Langman</name></author><author><name sortKey="Fraser, Paul E" sort="Fraser, Paul E" uniqKey="Fraser P" first="Paul E" last="Fraser">Paul E. Fraser</name></author><author><name sortKey="Tandon, Anurag" sort="Tandon, Anurag" uniqKey="Tandon A" first="Anurag" last="Tandon">Anurag Tandon</name></author></analytic><series><title level="j">The Journal of biological chemistry</title><idno type="eISSN">1083-351X</idno><imprint><date when="2013" type="published">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Brain (metabolism)</term><term>Cell Line, Tumor</term><term>Cell Membrane (metabolism)</term><term>Cytosol (metabolism)</term><term>Epitopes (chemistry)</term><term>Glycerol (chemistry)</term><term>Guanosine Triphosphate (metabolism)</term><term>HSP90 Heat-Shock Proteins (metabolism)</term><term>Humans</term><term>Mice</term><term>Mice, Transgenic</term><term>Models, Biological</term><term>Neurodegenerative Diseases (metabolism)</term><term>Neurons (metabolism)</term><term>Subcellular Fractions (metabolism)</term><term>Synapses (metabolism)</term><term>Synaptosomes (metabolism)</term><term>alpha-Synuclein (chemistry)</term><term>alpha-Synuclein (metabolism)</term><term>rab3A GTP-Binding Protein (metabolism)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Epitopes</term><term>Glycerol</term><term>alpha-Synuclein</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Brain</term><term>Cell Membrane</term><term>Cytosol</term><term>Guanosine Triphosphate</term><term>HSP90 Heat-Shock Proteins</term><term>Neurodegenerative Diseases</term><term>Neurons</term><term>Subcellular Fractions</term><term>Synapses</term><term>Synaptosomes</term><term>alpha-Synuclein</term><term>rab3A GTP-Binding Protein</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Line, Tumor</term><term>Humans</term><term>Mice</term><term>Mice, Transgenic</term><term>Models, Biological</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">α-Synuclein is an abundant presynaptic protein and a primary component of Lewy bodies in Parkinson disease. Although its pathogenic role remains unclear, in healthy nerve terminals α-synuclein undergoes a cycle of membrane binding and dissociation. An α-synuclein binding assay was used to screen for vesicle proteins involved in α-synuclein membrane interactions and showed that antibodies directed to the Ras-related GTPase Rab3a and its chaperone RabGDI abrogated α-synuclein membrane binding. Biochemical analyses, including density gradient sedimentation and co-immunoprecipitation, suggested that α-synuclein interacts with membrane-associated GTP-bound Rab3a but not to cytosolic GDP-Rab3a. Accumulation of membrane-bound α-synuclein was induced by the expression of a GTPase-deficient Rab3a mutant, by a dominant-negative GDP dissociation inhibitor mutant unable to recycle Rab3a off membranes, and by Hsp90 inhibitors, radicicol and geldanamycin, which are known to inhibit Rab3a dissociation from membranes. Thus, all treatments that inhibited Rab3a recycling also increased α-synuclein sequestration on intracellular membranes. Our results suggest that membrane-bound GTP-Rab3a stabilizes α-synuclein on synaptic vesicles and that the GDP dissociation inhibitor·Hsp90 complex that controls Rab3a membrane dissociation also regulates α-synuclein dissociation during synaptic activity.</div></front></TEI></pubmed></double></record>Pour manipuler ce document sous Unix (Dilib)
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