The Ca2+/Mn2+ ion-pump PMR1 links elevation of cytosolic Ca2+ levels to α-synuclein toxicity in Parkinson's disease models
Identifieur interne : 001097 ( Main/Merge ); précédent : 001096; suivant : 001098The Ca2+/Mn2+ ion-pump PMR1 links elevation of cytosolic Ca2+ levels to α-synuclein toxicity in Parkinson's disease models
Auteurs : S. Büttner [Autriche] ; L. Faes [Belgique] ; W N Reichelt [Autriche] ; F. Broeskamp [Autriche] ; L. Habernig [Autriche] ; S. Benke [Autriche] ; N. Kourtis [Grèce] ; D. Ruli [Autriche] ; D. Carmona-Gutierrez [Autriche] ; T. Eisenberg [Autriche] ; P. D'Hooge [Belgique] ; R. Ghillebert [Belgique] ; V. Franssens [Belgique] ; A. Harger [Autriche] ; T R Pieber [Autriche] ; P. Freudenberger [Autriche] ; G. Kroemer [France] ; S J Sigrist [Allemagne] ; J. Winderickx [Belgique] ; G. Callewaert [Belgique] ; N. Tavernarakis [Grèce] ; F. Madeo [Autriche]Source :
- Cell Death and Differentiation [ 1350-9047 ] ; 2012.
Abstract
Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons, which arises from a yet elusive concurrence between genetic and environmental factors. The protein
Url:
DOI: 10.1038/cdd.2012.142
PubMed: 23154387
PubMed Central: 3569987
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PMC:3569987Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">The Ca<sup>2+</sup>
/Mn<sup>2+</sup>
ion-pump PMR1 links elevation of cytosolic Ca<sup>2+</sup>
levels to <italic>α</italic>
-synuclein toxicity in Parkinson's disease models</title>
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<author><name sortKey="Carmona Gutierrez, D" sort="Carmona Gutierrez, D" uniqKey="Carmona Gutierrez D" first="D" last="Carmona-Gutierrez">D. Carmona-Gutierrez</name>
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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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</nlm:aff>
<country xml:lang="fr">Autriche</country>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">The Ca<sup>2+</sup>
/Mn<sup>2+</sup>
ion-pump PMR1 links elevation of cytosolic Ca<sup>2+</sup>
levels to <italic>α</italic>
-synuclein toxicity in Parkinson's disease models</title>
<author><name sortKey="Buttner, S" sort="Buttner, S" uniqKey="Buttner S" first="S" last="Büttner">S. Büttner</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Institute of Molecular Biosciences; University of Graz</institution>
; Graz,<country>Austria</country>
</nlm:aff>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Faes, L" sort="Faes, L" uniqKey="Faes L" first="L" last="Faes">L. Faes</name>
<affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Research Group Neurodegeneration; Katholieke Universiteit Leuven Campus Kortrijk</institution>
, Kortrijk,<country>Belgium</country>
</nlm:aff>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Functional Biology; Katholieke Universiteit Leuven</institution>
, Leuven,<country>Belgium</country>
</nlm:aff>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Reichelt, W N" sort="Reichelt, W N" uniqKey="Reichelt W" first="W N" last="Reichelt">W N Reichelt</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Institute of Molecular Biosciences; University of Graz</institution>
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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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</nlm:aff>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Habernig, L" sort="Habernig, L" uniqKey="Habernig L" first="L" last="Habernig">L. Habernig</name>
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; Graz,<country>Austria</country>
</nlm:aff>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Benke, S" sort="Benke, S" uniqKey="Benke S" first="S" last="Benke">S. Benke</name>
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</nlm:aff>
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<author><name sortKey="Kourtis, N" sort="Kourtis, N" uniqKey="Kourtis N" first="N" last="Kourtis">N. Kourtis</name>
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, Crete,<country>Greece</country>
</nlm:aff>
<country xml:lang="fr">Grèce</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Ruli, D" sort="Ruli, D" uniqKey="Ruli D" first="D" last="Ruli">D. Ruli</name>
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</nlm:aff>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Carmona Gutierrez, D" sort="Carmona Gutierrez, D" uniqKey="Carmona Gutierrez D" first="D" last="Carmona-Gutierrez">D. Carmona-Gutierrez</name>
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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="D Hooge, P" sort="D Hooge, P" uniqKey="D Hooge P" first="P" last="D'Hooge">P. D'Hooge</name>
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</nlm:aff>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Ghillebert, R" sort="Ghillebert, R" uniqKey="Ghillebert R" first="R" last="Ghillebert">R. Ghillebert</name>
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, Leuven,<country>Belgium</country>
</nlm:aff>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Franssens, V" sort="Franssens, V" uniqKey="Franssens V" first="V" last="Franssens">V. Franssens</name>
<affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Functional Biology; Katholieke Universiteit Leuven</institution>
, Leuven,<country>Belgium</country>
</nlm:aff>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Harger, A" sort="Harger, A" uniqKey="Harger A" first="A" last="Harger">A. Harger</name>
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, Graz,<country>Austria</country>
</nlm:aff>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
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<author><name sortKey="Pieber, T R" sort="Pieber, T R" uniqKey="Pieber T" first="T R" last="Pieber">T R Pieber</name>
<affiliation wicri:level="1"><nlm:aff id="aff5"><institution>Department of Internal Medicine, Medical University Graz</institution>
, Graz,<country>Austria</country>
</nlm:aff>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Freudenberger, P" sort="Freudenberger, P" uniqKey="Freudenberger P" first="P" last="Freudenberger">P. Freudenberger</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Institute of Molecular Biosciences; University of Graz</institution>
; Graz,<country>Austria</country>
</nlm:aff>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Kroemer, G" sort="Kroemer, G" uniqKey="Kroemer G" first="G" last="Kroemer">G. Kroemer</name>
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, 94805 Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff7"><institution>Metabolomics Platform, Institut Gustave Roussy</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff8"><institution>Centre de Recherche des Cordeliers</institution>
, Paris,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff9"><institution>Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP</institution>
, Paris,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff10"><institution>Université Paris Descartes, Sorbonne Paris Cité</institution>
, Paris,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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</author>
<author><name sortKey="Sigrist, S J" sort="Sigrist, S J" uniqKey="Sigrist S" first="S J" last="Sigrist">S J Sigrist</name>
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</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Winderickx, J" sort="Winderickx, J" uniqKey="Winderickx J" first="J" last="Winderickx">J. Winderickx</name>
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, Leuven,<country>Belgium</country>
</nlm:aff>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
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<author><name sortKey="Callewaert, G" sort="Callewaert, G" uniqKey="Callewaert G" first="G" last="Callewaert">G. Callewaert</name>
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</nlm:aff>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
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<author><name sortKey="Tavernarakis, N" sort="Tavernarakis, N" uniqKey="Tavernarakis N" first="N" last="Tavernarakis">N. Tavernarakis</name>
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, Crete,<country>Greece</country>
</nlm:aff>
<country xml:lang="fr">Grèce</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
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<author><name sortKey="Madeo, F" sort="Madeo, F" uniqKey="Madeo F" first="F" last="Madeo">F. Madeo</name>
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; Graz,<country>Austria</country>
</nlm:aff>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
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</analytic>
<series><title level="j">Cell Death and Differentiation</title>
<idno type="ISSN">1350-9047</idno>
<idno type="eISSN">1476-5403</idno>
<imprint><date when="2012">2012</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons, which arises from a yet elusive concurrence between genetic and environmental factors. The protein <italic>α</italic>
-synuclein (<italic>α</italic>
Syn), the principle toxic effector in PD, has been shown to interfere with neuronal Ca<sup>2+</sup>
fluxes, arguing for an involvement of deregulated Ca<sup>2+</sup>
homeostasis in this neuronal demise. Here, we identify the Golgi-resident Ca<sup>2+</sup>
/Mn<sup>2+</sup>
ATPase PMR1 (plasma membrane-related Ca<sup>2+</sup>
-ATPase 1) as a phylogenetically conserved mediator of <italic>α</italic>
Syn-driven changes in Ca<sup>2+</sup>
homeostasis and cytotoxicity. Expression of <italic>α</italic>
Syn in yeast resulted in elevated cytosolic Ca<sup>2+</sup>
levels and increased cell death, both of which could be inhibited by deletion of PMR1. Accordingly, absence of PMR1 prevented <italic>α</italic>
Syn-induced loss of dopaminergic neurons in nematodes and flies. In addition, <italic>α</italic>
Syn failed to compromise locomotion and survival of flies when PMR1 was absent. In conclusion, the <italic>α</italic>
Syn-driven rise of cytosolic Ca<sup>2+</sup>
levels is pivotal for its cytotoxicity and requires PMR1.</p>
</div>
</front>
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