ParkinsonFranceV1, Main, Exploration, bibRecord, 000112

α-Synuclein is a Novel Microtubule Dynamase.

Identifieur interne : 000112 ( Main/Exploration ); précédent : 000111; suivant : 000113

α-Synuclein is a Novel Microtubule Dynamase.

Auteurs : Daniele Cartelli [Italie] ; Alessandro Aliverti [Italie] ; Alberto Barbiroli [Italie] ; Carlo Santambrogio [Italie] ; Enzio M. Ragg [Italie] ; Francesca V M. Casagrande [Italie] ; Francesca Cantele [Italie] ; Silvia Beltramone [Italie] ; Jacopo Marangon [Italie] ; Carmelita De Gregorio [Italie] ; Vittorio Pandini [Italie] ; Marco Emanuele [Italie] ; Evelina Chieregatti [Italie] ; Stefano Pieraccini [Italie] ; Staffan Holmqvist [Suède] ; Luigi Bubacco [Italie] ; Laurent Roybon [Suède] ; Gianni Pezzoli [Italie] ; Rita Grandori [Italie] ; Isabelle Arnal [France] ; Graziella Cappelletti [Italie]

Source :

Scientific reports [ 2045-2322 ] ; 2016.

RBID : pubmed:27628239

Abstract

α-Synuclein is a presynaptic protein associated to Parkinson's disease, which is unstructured when free in the cytoplasm and adopts α helical conformation when bound to vesicles. After decades of intense studies, α-Synuclein physiology is still difficult to clear up due to its interaction with multiple partners and its involvement in a pletora of neuronal functions. Here, we looked at the remarkably neglected interplay between α-Synuclein and microtubules, which potentially impacts on synaptic functionality. In order to identify the mechanisms underlying these actions, we investigated the interaction between purified α-Synuclein and tubulin. We demonstrated that α-Synuclein binds to microtubules and tubulin α2β2 tetramer; the latter interaction inducing the formation of helical segment(s) in the α-Synuclein polypeptide. This structural change seems to enable α-Synuclein to promote microtubule nucleation and to enhance microtubule growth rate and catastrophe frequency, both in vitro and in cell. We also showed that Parkinson's disease-linked α-Synuclein variants do not undergo tubulin-induced folding and cause tubulin aggregation rather than polymerization. Our data enable us to propose α-Synuclein as a novel, foldable, microtubule-dynamase, which influences microtubule organisation through its binding to tubulin and its regulating effects on microtubule nucleation and dynamics.

DOI: 10.1038/srep33289
PubMed: 27628239

Affiliations:

Le document en format XML

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<author><name sortKey="Marangon, Jacopo" sort="Marangon, Jacopo" uniqKey="Marangon J" first="Jacopo" last="Marangon">Jacopo Marangon</name>
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<author><name sortKey="De Gregorio, Carmelita" sort="De Gregorio, Carmelita" uniqKey="De Gregorio C" first="Carmelita" last="De Gregorio">Carmelita De Gregorio</name>
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<author><name sortKey="Pandini, Vittorio" sort="Pandini, Vittorio" uniqKey="Pandini V" first="Vittorio" last="Pandini">Vittorio Pandini</name>
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<author><name sortKey="Emanuele, Marco" sort="Emanuele, Marco" uniqKey="Emanuele M" first="Marco" last="Emanuele">Marco Emanuele</name>
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<author><name sortKey="Holmqvist, Staffan" sort="Holmqvist, Staffan" uniqKey="Holmqvist S" first="Staffan" last="Holmqvist">Staffan Holmqvist</name>
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<author><name sortKey="Roybon, Laurent" sort="Roybon, Laurent" uniqKey="Roybon L" first="Laurent" last="Roybon">Laurent Roybon</name>
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<author><name sortKey="Grandori, Rita" sort="Grandori, Rita" uniqKey="Grandori R" first="Rita" last="Grandori">Rita Grandori</name>
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<author><name sortKey="Arnal, Isabelle" sort="Arnal, Isabelle" uniqKey="Arnal I" first="Isabelle" last="Arnal">Isabelle Arnal</name>
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<author><name sortKey="Cartelli, Daniele" sort="Cartelli, Daniele" uniqKey="Cartelli D" first="Daniele" last="Cartelli">Daniele Cartelli</name>
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<author><name sortKey="Aliverti, Alessandro" sort="Aliverti, Alessandro" uniqKey="Aliverti A" first="Alessandro" last="Aliverti">Alessandro Aliverti</name>
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<author><name sortKey="Barbiroli, Alberto" sort="Barbiroli, Alberto" uniqKey="Barbiroli A" first="Alberto" last="Barbiroli">Alberto Barbiroli</name>
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<author><name sortKey="Santambrogio, Carlo" sort="Santambrogio, Carlo" uniqKey="Santambrogio C" first="Carlo" last="Santambrogio">Carlo Santambrogio</name>
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<author><name sortKey="Ragg, Enzio M" sort="Ragg, Enzio M" uniqKey="Ragg E" first="Enzio M" last="Ragg">Enzio M. Ragg</name>
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<author><name sortKey="Casagrande, Francesca V M" sort="Casagrande, Francesca V M" uniqKey="Casagrande F" first="Francesca V M" last="Casagrande">Francesca V M. Casagrande</name>
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<author><name sortKey="Cantele, Francesca" sort="Cantele, Francesca" uniqKey="Cantele F" first="Francesca" last="Cantele">Francesca Cantele</name>
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<author><name sortKey="Beltramone, Silvia" sort="Beltramone, Silvia" uniqKey="Beltramone S" first="Silvia" last="Beltramone">Silvia Beltramone</name>
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<author><name sortKey="Marangon, Jacopo" sort="Marangon, Jacopo" uniqKey="Marangon J" first="Jacopo" last="Marangon">Jacopo Marangon</name>
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<author><name sortKey="De Gregorio, Carmelita" sort="De Gregorio, Carmelita" uniqKey="De Gregorio C" first="Carmelita" last="De Gregorio">Carmelita De Gregorio</name>
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<country xml:lang="fr">Italie</country>
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<author><name sortKey="Pandini, Vittorio" sort="Pandini, Vittorio" uniqKey="Pandini V" first="Vittorio" last="Pandini">Vittorio Pandini</name>
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<country xml:lang="fr">Italie</country>
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<author><name sortKey="Emanuele, Marco" sort="Emanuele, Marco" uniqKey="Emanuele M" first="Marco" last="Emanuele">Marco Emanuele</name>
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<country xml:lang="fr">Italie</country>
<wicri:regionArea>Dept. Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genova</wicri:regionArea>
<wicri:noRegion>Genova</wicri:noRegion>
</affiliation>
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<author><name sortKey="Chieregatti, Evelina" sort="Chieregatti, Evelina" uniqKey="Chieregatti E" first="Evelina" last="Chieregatti">Evelina Chieregatti</name>
<affiliation wicri:level="1"><nlm:affiliation>Dept. Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genova, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Dept. Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genova</wicri:regionArea>
<wicri:noRegion>Genova</wicri:noRegion>
</affiliation>
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<author><name sortKey="Pieraccini, Stefano" sort="Pieraccini, Stefano" uniqKey="Pieraccini S" first="Stefano" last="Pieraccini">Stefano Pieraccini</name>
<affiliation wicri:level="1"><nlm:affiliation>Dept. Chemistry, Università degli Studi di Milano, Milano, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Dept. Chemistry, Università degli Studi di Milano, Milano</wicri:regionArea>
<wicri:noRegion>Milano</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Holmqvist, Staffan" sort="Holmqvist, Staffan" uniqKey="Holmqvist S" first="Staffan" last="Holmqvist">Staffan Holmqvist</name>
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<country xml:lang="fr">Suède</country>
<wicri:regionArea>Stem Cell laboratory for CNS Disease Modeling, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, Lund</wicri:regionArea>
<wicri:noRegion>Lund</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Bubacco, Luigi" sort="Bubacco, Luigi" uniqKey="Bubacco L" first="Luigi" last="Bubacco">Luigi Bubacco</name>
<affiliation wicri:level="1"><nlm:affiliation>Dept. Biology, University of Padova, Padova, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Dept. Biology, University of Padova, Padova</wicri:regionArea>
<wicri:noRegion>Padova</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Roybon, Laurent" sort="Roybon, Laurent" uniqKey="Roybon L" first="Laurent" last="Roybon">Laurent Roybon</name>
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<country xml:lang="fr">Suède</country>
<wicri:regionArea>Stem Cell laboratory for CNS Disease Modeling, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, Lund</wicri:regionArea>
<wicri:noRegion>Lund</wicri:noRegion>
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</author>
<author><name sortKey="Pezzoli, Gianni" sort="Pezzoli, Gianni" uniqKey="Pezzoli G" first="Gianni" last="Pezzoli">Gianni Pezzoli</name>
<affiliation wicri:level="1"><nlm:affiliation>Parkinson Institute, ASST G. Pini-CTO, ex ICP, Milano, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Parkinson Institute, ASST G. Pini-CTO, ex ICP, Milano</wicri:regionArea>
<wicri:noRegion>Milano</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Grandori, Rita" sort="Grandori, Rita" uniqKey="Grandori R" first="Rita" last="Grandori">Rita Grandori</name>
<affiliation wicri:level="1"><nlm:affiliation>Dept. Biotecnology and Biosciences, Università degli Studi di Milano-Bicocca, Milano, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Dept. Biotecnology and Biosciences, Università degli Studi di Milano-Bicocca, Milano</wicri:regionArea>
<wicri:noRegion>Milano</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Arnal, Isabelle" sort="Arnal, Isabelle" uniqKey="Arnal I" first="Isabelle" last="Arnal">Isabelle Arnal</name>
<affiliation wicri:level="3"><nlm:affiliation>Grenoble Institut des Neurosciences, Grenoble, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Grenoble Institut des Neurosciences, Grenoble</wicri:regionArea>
<placeName><region type="region">Auvergne-Rhône-Alpes</region>
<region type="old region">Rhône-Alpes</region>
<settlement type="city">Grenoble</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Cappelletti, Graziella" sort="Cappelletti, Graziella" uniqKey="Cappelletti G" first="Graziella" last="Cappelletti">Graziella Cappelletti</name>
<affiliation wicri:level="1"><nlm:affiliation>Dept. Biosciences, Università degli Studi di Milano, Milano, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Dept. Biosciences, Università degli Studi di Milano, Milano</wicri:regionArea>
<wicri:noRegion>Milano</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">Scientific reports</title>
<idno type="eISSN">2045-2322</idno>
<imprint><date when="2016" type="published">2016</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">α-Synuclein is a presynaptic protein associated to Parkinson's disease, which is unstructured when free in the cytoplasm and adopts α helical conformation when bound to vesicles. After decades of intense studies, α-Synuclein physiology is still difficult to clear up due to its interaction with multiple partners and its involvement in a pletora of neuronal functions. Here, we looked at the remarkably neglected interplay between α-Synuclein and microtubules, which potentially impacts on synaptic functionality. In order to identify the mechanisms underlying these actions, we investigated the interaction between purified α-Synuclein and tubulin. We demonstrated that α-Synuclein binds to microtubules and tubulin α2β2 tetramer; the latter interaction inducing the formation of helical segment(s) in the α-Synuclein polypeptide. This structural change seems to enable α-Synuclein to promote microtubule nucleation and to enhance microtubule growth rate and catastrophe frequency, both in vitro and in cell. We also showed that Parkinson's disease-linked α-Synuclein variants do not undergo tubulin-induced folding and cause tubulin aggregation rather than polymerization. Our data enable us to propose α-Synuclein as a novel, foldable, microtubule-dynamase, which influences microtubule organisation through its binding to tubulin and its regulating effects on microtubule nucleation and dynamics.</div>
</front>
</TEI>
<affiliations><list><country><li>France</li>
<li>Italie</li>
<li>Suède</li>
</country>
<region><li>Auvergne-Rhône-Alpes</li>
<li>Rhône-Alpes</li>
</region>
<settlement><li>Grenoble</li>
</settlement>
</list>
<tree><country name="Italie"><noRegion><name sortKey="Cartelli, Daniele" sort="Cartelli, Daniele" uniqKey="Cartelli D" first="Daniele" last="Cartelli">Daniele Cartelli</name>
</noRegion>
<name sortKey="Aliverti, Alessandro" sort="Aliverti, Alessandro" uniqKey="Aliverti A" first="Alessandro" last="Aliverti">Alessandro Aliverti</name>
<name sortKey="Barbiroli, Alberto" sort="Barbiroli, Alberto" uniqKey="Barbiroli A" first="Alberto" last="Barbiroli">Alberto Barbiroli</name>
<name sortKey="Beltramone, Silvia" sort="Beltramone, Silvia" uniqKey="Beltramone S" first="Silvia" last="Beltramone">Silvia Beltramone</name>
<name sortKey="Bubacco, Luigi" sort="Bubacco, Luigi" uniqKey="Bubacco L" first="Luigi" last="Bubacco">Luigi Bubacco</name>
<name sortKey="Cantele, Francesca" sort="Cantele, Francesca" uniqKey="Cantele F" first="Francesca" last="Cantele">Francesca Cantele</name>
<name sortKey="Cappelletti, Graziella" sort="Cappelletti, Graziella" uniqKey="Cappelletti G" first="Graziella" last="Cappelletti">Graziella Cappelletti</name>
<name sortKey="Casagrande, Francesca V M" sort="Casagrande, Francesca V M" uniqKey="Casagrande F" first="Francesca V M" last="Casagrande">Francesca V M. Casagrande</name>
<name sortKey="Chieregatti, Evelina" sort="Chieregatti, Evelina" uniqKey="Chieregatti E" first="Evelina" last="Chieregatti">Evelina Chieregatti</name>
<name sortKey="De Gregorio, Carmelita" sort="De Gregorio, Carmelita" uniqKey="De Gregorio C" first="Carmelita" last="De Gregorio">Carmelita De Gregorio</name>
<name sortKey="Emanuele, Marco" sort="Emanuele, Marco" uniqKey="Emanuele M" first="Marco" last="Emanuele">Marco Emanuele</name>
<name sortKey="Grandori, Rita" sort="Grandori, Rita" uniqKey="Grandori R" first="Rita" last="Grandori">Rita Grandori</name>
<name sortKey="Marangon, Jacopo" sort="Marangon, Jacopo" uniqKey="Marangon J" first="Jacopo" last="Marangon">Jacopo Marangon</name>
<name sortKey="Pandini, Vittorio" sort="Pandini, Vittorio" uniqKey="Pandini V" first="Vittorio" last="Pandini">Vittorio Pandini</name>
<name sortKey="Pezzoli, Gianni" sort="Pezzoli, Gianni" uniqKey="Pezzoli G" first="Gianni" last="Pezzoli">Gianni Pezzoli</name>
<name sortKey="Pieraccini, Stefano" sort="Pieraccini, Stefano" uniqKey="Pieraccini S" first="Stefano" last="Pieraccini">Stefano Pieraccini</name>
<name sortKey="Ragg, Enzio M" sort="Ragg, Enzio M" uniqKey="Ragg E" first="Enzio M" last="Ragg">Enzio M. Ragg</name>
<name sortKey="Santambrogio, Carlo" sort="Santambrogio, Carlo" uniqKey="Santambrogio C" first="Carlo" last="Santambrogio">Carlo Santambrogio</name>
</country>
<country name="Suède"><noRegion><name sortKey="Holmqvist, Staffan" sort="Holmqvist, Staffan" uniqKey="Holmqvist S" first="Staffan" last="Holmqvist">Staffan Holmqvist</name>
</noRegion>
<name sortKey="Roybon, Laurent" sort="Roybon, Laurent" uniqKey="Roybon L" first="Laurent" last="Roybon">Laurent Roybon</name>
</country>
<country name="France"><region name="Auvergne-Rhône-Alpes"><name sortKey="Arnal, Isabelle" sort="Arnal, Isabelle" uniqKey="Arnal I" first="Isabelle" last="Arnal">Isabelle Arnal</name>
</region>
</country>
</tree>
</affiliations>
</record>

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La maladie de Parkinson en France (serveur d'exploration)

α-Synuclein is a Novel Microtubule Dynamase.

α-Synuclein is a Novel Microtubule Dynamase.

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