Identification of ciliary neurotrophic factor receptor α as a mediator of neurotoxicity induced by α‐synuclein
Identifieur interne : 001D30 ( Main/Merge ); précédent : 001D29; suivant : 001D31Identification of ciliary neurotrophic factor receptor α as a mediator of neurotoxicity induced by α‐synuclein
Auteurs : Jun Liu [République populaire de Chine, États-Unis] ; Min Shi [États-Unis] ; Zhen Hong [République populaire de Chine] ; Jianpeng Zhang [États-Unis] ; Joshua Bradner [États-Unis] ; Thomas Quinn [États-Unis] ; Richard P. Beyer [États-Unis] ; Patrick L. Mcgeer [Canada] ; Shengdi Chen [République populaire de Chine] ; Jing Zhang [États-Unis]Source :
- PROTEOMICS [ 1615-9853 ] ; 2010-06.
English descriptors
- KwdEn :
Abstract
Accumulating evidence suggests that extracellular α‐synuclein (eSNCA) plays an important role in the pathogenesis of Parkinson's disease or related synucleinopathies by inducing neurotoxicity directly or indirectly via microglial or astroglial activation. However, the mechanisms by which this occurs remain to be characterized. To explore these mechanisms, we combined three biochemical techniques – stable isotope labeling of amino acid in cell cultures (SILAC), biotin labeling of plasma membrane proteins followed by affinity purification, and analysis of unique proteins binding to SNCA peptides on membrane arrays. The SILAC proteomic analysis identified 457 proteins, of which, 245 or 172 proteins belonged to membrane or membrane associated proteins, depending on the various bioinformatics tools used for interpretation. In dopamine neuronal cells treated with eSNCA, the levels of 86 membrane proteins were increased and 35 were decreased compared with untreated cells. In peptide array analysis, 127 proteins were identified as possibly interacting with eSNCA. Of those, seven proteins were overlapped with the membrane proteins that displayed alterations in relative abundance after eSNCA treatment. One was ciliary neurotrophic factor receptor, which appeared to modulate eSNCA‐mediated neurotoxicity via mechanisms related to JAK1/STAT3 signaling but independent of eSNCA endocytosis.
Url:
- https://api-v5.istex.fr/document/A89D2BF6844C4B72FCF5B8F4B2B50916A9F89687/fulltext/pdf
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3013276
DOI: 10.1002/pmic.200900745
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<PMC><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Identification of ciliary neurotrophic factor receptor alpha as a mediator of neurotoxicity induced by α-synuclein</title>
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<affiliation wicri:level="1"><nlm:aff id="A1">Department of Neurology & Institute of Neurology, Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Neurology & Institute of Neurology, Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai</wicri:regionArea>
<wicri:noRegion>Shanghai</wicri:noRegion>
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<affiliation wicri:level="2"><nlm:aff id="A2">Department of Pathology, University of Washington School of Medicine, Seattle, Washington, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology, University of Washington School of Medicine, Seattle, Washington</wicri:regionArea>
<placeName><region type="state">Washington (État)</region>
</placeName>
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</author>
<author><name sortKey="Shi, Min" sort="Shi, Min" uniqKey="Shi M" first="Min" last="Shi">Min Shi</name>
<affiliation wicri:level="2"><nlm:aff id="A2">Department of Pathology, University of Washington School of Medicine, Seattle, Washington, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology, University of Washington School of Medicine, Seattle, Washington</wicri:regionArea>
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</author>
<author><name sortKey="Hong, Zhen" sort="Hong, Zhen" uniqKey="Hong Z" first="Zhen" last="Hong">Zhen Hong</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Department of Neurology & Institute of Neurology, Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Neurology & Institute of Neurology, Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai</wicri:regionArea>
<wicri:noRegion>Shanghai</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Zhang, Jianpeng" sort="Zhang, Jianpeng" uniqKey="Zhang J" first="Jianpeng" last="Zhang">Jianpeng Zhang</name>
<affiliation wicri:level="2"><nlm:aff id="A2">Department of Pathology, University of Washington School of Medicine, Seattle, Washington, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology, University of Washington School of Medicine, Seattle, Washington</wicri:regionArea>
<placeName><region type="state">Washington (État)</region>
</placeName>
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</author>
<author><name sortKey="Bradner, Joshua" sort="Bradner, Joshua" uniqKey="Bradner J" first="Joshua" last="Bradner">Joshua Bradner</name>
<affiliation wicri:level="2"><nlm:aff id="A2">Department of Pathology, University of Washington School of Medicine, Seattle, Washington, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology, University of Washington School of Medicine, Seattle, Washington</wicri:regionArea>
<placeName><region type="state">Washington (État)</region>
</placeName>
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<author><name sortKey="Quinn, Thomas" sort="Quinn, Thomas" uniqKey="Quinn T" first="Thomas" last="Quinn">Thomas Quinn</name>
<affiliation wicri:level="2"><nlm:aff id="A2">Department of Pathology, University of Washington School of Medicine, Seattle, Washington, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology, University of Washington School of Medicine, Seattle, Washington</wicri:regionArea>
<placeName><region type="state">Washington (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Beyer, Richard P" sort="Beyer, Richard P" uniqKey="Beyer R" first="Richard P." last="Beyer">Richard P. Beyer</name>
<affiliation wicri:level="4"><nlm:aff id="A3">Department of Environmental & Occupational Health Sciences, University of Washington, Seattle, Washington, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Environmental & Occupational Health Sciences, University of Washington, Seattle, Washington</wicri:regionArea>
<placeName><region type="state">Washington (État)</region>
<settlement type="city">Seattle</settlement>
</placeName>
<orgName type="university">Université de Washington</orgName>
</affiliation>
</author>
<author><name sortKey="Mcgeer, Patrick L" sort="Mcgeer, Patrick L" uniqKey="Mcgeer P" first="Patrick L." last="Mcgeer">Patrick L. Mcgeer</name>
<affiliation wicri:level="1"><nlm:aff id="A4">Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, BC, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, BC</wicri:regionArea>
<wicri:noRegion>BC</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Chen, Shengdi" sort="Chen, Shengdi" uniqKey="Chen S" first="Shengdi" last="Chen">Shengdi Chen</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Department of Neurology & Institute of Neurology, Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Neurology & Institute of Neurology, Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai</wicri:regionArea>
<wicri:noRegion>Shanghai</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Zhang, Jing" sort="Zhang, Jing" uniqKey="Zhang J" first="Jing" last="Zhang">Jing Zhang</name>
<affiliation wicri:level="2"><nlm:aff id="A2">Department of Pathology, University of Washington School of Medicine, Seattle, Washington, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology, University of Washington School of Medicine, Seattle, Washington</wicri:regionArea>
<placeName><region type="state">Washington (État)</region>
</placeName>
</affiliation>
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<idno type="doi">10.1002/pmic.200900745</idno>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Identification of ciliary neurotrophic factor receptor alpha as a mediator of neurotoxicity induced by α-synuclein</title>
<author><name sortKey="Liu, Jun" sort="Liu, Jun" uniqKey="Liu J" first="Jun" last="Liu">Jun Liu</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Department of Neurology & Institute of Neurology, Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Neurology & Institute of Neurology, Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai</wicri:regionArea>
<wicri:noRegion>Shanghai</wicri:noRegion>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A2">Department of Pathology, University of Washington School of Medicine, Seattle, Washington, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology, University of Washington School of Medicine, Seattle, Washington</wicri:regionArea>
<placeName><region type="state">Washington (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Shi, Min" sort="Shi, Min" uniqKey="Shi M" first="Min" last="Shi">Min Shi</name>
<affiliation wicri:level="2"><nlm:aff id="A2">Department of Pathology, University of Washington School of Medicine, Seattle, Washington, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology, University of Washington School of Medicine, Seattle, Washington</wicri:regionArea>
<placeName><region type="state">Washington (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Hong, Zhen" sort="Hong, Zhen" uniqKey="Hong Z" first="Zhen" last="Hong">Zhen Hong</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Department of Neurology & Institute of Neurology, Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Neurology & Institute of Neurology, Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai</wicri:regionArea>
<wicri:noRegion>Shanghai</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Zhang, Jianpeng" sort="Zhang, Jianpeng" uniqKey="Zhang J" first="Jianpeng" last="Zhang">Jianpeng Zhang</name>
<affiliation wicri:level="2"><nlm:aff id="A2">Department of Pathology, University of Washington School of Medicine, Seattle, Washington, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology, University of Washington School of Medicine, Seattle, Washington</wicri:regionArea>
<placeName><region type="state">Washington (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bradner, Joshua" sort="Bradner, Joshua" uniqKey="Bradner J" first="Joshua" last="Bradner">Joshua Bradner</name>
<affiliation wicri:level="2"><nlm:aff id="A2">Department of Pathology, University of Washington School of Medicine, Seattle, Washington, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology, University of Washington School of Medicine, Seattle, Washington</wicri:regionArea>
<placeName><region type="state">Washington (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Quinn, Thomas" sort="Quinn, Thomas" uniqKey="Quinn T" first="Thomas" last="Quinn">Thomas Quinn</name>
<affiliation wicri:level="2"><nlm:aff id="A2">Department of Pathology, University of Washington School of Medicine, Seattle, Washington, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology, University of Washington School of Medicine, Seattle, Washington</wicri:regionArea>
<placeName><region type="state">Washington (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Beyer, Richard P" sort="Beyer, Richard P" uniqKey="Beyer R" first="Richard P." last="Beyer">Richard P. Beyer</name>
<affiliation wicri:level="4"><nlm:aff id="A3">Department of Environmental & Occupational Health Sciences, University of Washington, Seattle, Washington, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Environmental & Occupational Health Sciences, University of Washington, Seattle, Washington</wicri:regionArea>
<placeName><region type="state">Washington (État)</region>
<settlement type="city">Seattle</settlement>
</placeName>
<orgName type="university">Université de Washington</orgName>
</affiliation>
</author>
<author><name sortKey="Mcgeer, Patrick L" sort="Mcgeer, Patrick L" uniqKey="Mcgeer P" first="Patrick L." last="Mcgeer">Patrick L. Mcgeer</name>
<affiliation wicri:level="1"><nlm:aff id="A4">Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, BC, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, BC</wicri:regionArea>
<wicri:noRegion>BC</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Chen, Shengdi" sort="Chen, Shengdi" uniqKey="Chen S" first="Shengdi" last="Chen">Shengdi Chen</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Department of Neurology & Institute of Neurology, Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Neurology & Institute of Neurology, Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai</wicri:regionArea>
<wicri:noRegion>Shanghai</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Zhang, Jing" sort="Zhang, Jing" uniqKey="Zhang J" first="Jing" last="Zhang">Jing Zhang</name>
<affiliation wicri:level="2"><nlm:aff id="A2">Department of Pathology, University of Washington School of Medicine, Seattle, Washington, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology, University of Washington School of Medicine, Seattle, Washington</wicri:regionArea>
<placeName><region type="state">Washington (État)</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">Proteomics</title>
<idno type="ISSN">1615-9853</idno>
<idno type="eISSN">1615-9861</idno>
<imprint><date when="2010">2010</date>
</imprint>
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<front><div type="abstract" xml:lang="en"><p id="P1">Accumulating evidence suggests that extracellular α-synuclein (eSNCA) plays an important role in the pathogenesis of Parkinson's disease (PD) or related synucleinopathies by inducing neurotoxicity directly or indirectly via microglial or astroglial activation. However, the mechanisms by which this occurs remain to be characterized. To explore these mechanisms, we combined three biochemical techniques - Stable Isotope Labeling of Amino acid in Cell cultures (SILAC); biotin labeling of plasma membrane proteins followed by affinity purification; and analysis of unique proteins binding to SNCA peptides on membrane arrays. The SILAC proteomic analysis identified 457 proteins, of which, 245 or 172 proteins belonged to membrane or membrane associated proteins, depending on the various bioinformatics tools used for interpretation. In dopamine neuronal cells treated with eSNCA, the levels of 86 membrane proteins were increased and 35 were decreased compared with untreated cells. In peptide array analysis, 127 proteins were identified as possibly interacting with eSNCA. Of those, seven proteins were overlapped with the membrane proteins that displayed alterations in relative abundance after eSNCA treatment. One was ciliary neurotrophic factor receptor alpha (CNTFR-α), which appeared to modulate eSNCA-mediated neurotoxicity via mechanisms related to JAK1/STAT3 signaling but independent of eSNCA endocytosis.</p>
</div>
</front>
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