α-Synuclein is a Novel Microtubule Dynamase.
Identifieur interne : 000087 ( PubMed/Corpus ); précédent : 000086; suivant : 000088α-Synuclein is a Novel Microtubule Dynamase.
Auteurs : Daniele Cartelli ; Alessandro Aliverti ; Alberto Barbiroli ; Carlo Santambrogio ; Enzio M. Ragg ; Francesca V M. Casagrande ; Francesca Cantele ; Silvia Beltramone ; Jacopo Marangon ; Carmelita De Gregorio ; Vittorio Pandini ; Marco Emanuele ; Evelina Chieregatti ; Stefano Pieraccini ; Staffan Holmqvist ; Luigi Bubacco ; Laurent Roybon ; Gianni Pezzoli ; Rita Grandori ; Isabelle Arnal ; Graziella CappellettiSource :
- Scientific reports [ 2045-2322 ] ; 2016.
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
Links to Exploration step
pubmed:27628239Le document en format XML
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<author><name sortKey="Pieraccini, Stefano" sort="Pieraccini, Stefano" uniqKey="Pieraccini S" first="Stefano" last="Pieraccini">Stefano Pieraccini</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="Bubacco, Luigi" sort="Bubacco, Luigi" uniqKey="Bubacco L" first="Luigi" last="Bubacco">Luigi Bubacco</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="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>
<affiliation><nlm:affiliation>Dept. Biosciences, Università degli Studi di Milano, Milano, Italy.</nlm:affiliation>
</affiliation>
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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>
<affiliation><nlm:affiliation>Dept. Biosciences, Università degli Studi di Milano, Milano, Italy.</nlm:affiliation>
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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>
<affiliation><nlm:affiliation>Dept. Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genova, Italy.</nlm:affiliation>
</affiliation>
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<author><name sortKey="Chieregatti, Evelina" sort="Chieregatti, Evelina" uniqKey="Chieregatti E" first="Evelina" last="Chieregatti">Evelina Chieregatti</name>
<affiliation><nlm:affiliation>Dept. Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genova, Italy.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Pieraccini, Stefano" sort="Pieraccini, Stefano" uniqKey="Pieraccini S" first="Stefano" last="Pieraccini">Stefano Pieraccini</name>
<affiliation><nlm:affiliation>Dept. Chemistry, Università degli Studi di Milano, Milano, Italy.</nlm:affiliation>
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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="Bubacco, Luigi" sort="Bubacco, Luigi" uniqKey="Bubacco L" first="Luigi" last="Bubacco">Luigi Bubacco</name>
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</affiliation>
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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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</affiliation>
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<author><name sortKey="Pezzoli, Gianni" sort="Pezzoli, Gianni" uniqKey="Pezzoli G" first="Gianni" last="Pezzoli">Gianni Pezzoli</name>
<affiliation><nlm:affiliation>Parkinson Institute, ASST G. Pini-CTO, ex ICP, Milano, Italy.</nlm:affiliation>
</affiliation>
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<author><name sortKey="Grandori, Rita" sort="Grandori, Rita" uniqKey="Grandori R" first="Rita" last="Grandori">Rita Grandori</name>
<affiliation><nlm:affiliation>Dept. Biotecnology and Biosciences, Università degli Studi di Milano-Bicocca, Milano, Italy.</nlm:affiliation>
</affiliation>
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<author><name sortKey="Arnal, Isabelle" sort="Arnal, Isabelle" uniqKey="Arnal I" first="Isabelle" last="Arnal">Isabelle Arnal</name>
<affiliation><nlm:affiliation>Grenoble Institut des Neurosciences, Grenoble, France.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Cappelletti, Graziella" sort="Cappelletti, Graziella" uniqKey="Cappelletti G" first="Graziella" last="Cappelletti">Graziella Cappelletti</name>
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<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>
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<Month>09</Month>
<Day>16</Day>
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<DateRevised><Year>2016</Year>
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<Abstract><AbstractText>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.</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Cartelli</LastName>
<ForeName>Daniele</ForeName>
<Initials>D</Initials>
<AffiliationInfo><Affiliation>Dept. Biosciences, Università degli Studi di Milano, Milano, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Aliverti</LastName>
<ForeName>Alessandro</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Dept. Biosciences, Università degli Studi di Milano, Milano, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Barbiroli</LastName>
<ForeName>Alberto</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Dept. of Food, Environmental and Nutritional Sciences, Università degli Studi di Milano, Milano, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Santambrogio</LastName>
<ForeName>Carlo</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>Dept. Biotecnology and Biosciences, Università degli Studi di Milano-Bicocca, Milano, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ragg</LastName>
<ForeName>Enzio M</ForeName>
<Initials>EM</Initials>
<AffiliationInfo><Affiliation>Dept. of Food, Environmental and Nutritional Sciences, Università degli Studi di Milano, Milano, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Casagrande</LastName>
<ForeName>Francesca V M</ForeName>
<Initials>FV</Initials>
<AffiliationInfo><Affiliation>Dept. Biosciences, Università degli Studi di Milano, Milano, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Cantele</LastName>
<ForeName>Francesca</ForeName>
<Initials>F</Initials>
<AffiliationInfo><Affiliation>Dept. Biosciences, Università degli Studi di Milano, Milano, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Beltramone</LastName>
<ForeName>Silvia</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Dept. Biosciences, Università degli Studi di Milano, Milano, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Marangon</LastName>
<ForeName>Jacopo</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Dept. Biosciences, Università degli Studi di Milano, Milano, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>De Gregorio</LastName>
<ForeName>Carmelita</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>Dept. Biosciences, Università degli Studi di Milano, Milano, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Pandini</LastName>
<ForeName>Vittorio</ForeName>
<Initials>V</Initials>
<AffiliationInfo><Affiliation>Dept. Biosciences, Università degli Studi di Milano, Milano, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Emanuele</LastName>
<ForeName>Marco</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Dept. Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genova, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Chieregatti</LastName>
<ForeName>Evelina</ForeName>
<Initials>E</Initials>
<AffiliationInfo><Affiliation>Dept. Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genova, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Pieraccini</LastName>
<ForeName>Stefano</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Dept. Chemistry, Università degli Studi di Milano, Milano, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Holmqvist</LastName>
<ForeName>Staffan</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Stem Cell laboratory for CNS Disease Modeling, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, Lund, Sweden.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Strategic Research Area MultiPark and Lund Stem Cell Center, Lund University, Lund, Sweden.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Bubacco</LastName>
<ForeName>Luigi</ForeName>
<Initials>L</Initials>
<AffiliationInfo><Affiliation>Dept. Biology, University of Padova, Padova, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Roybon</LastName>
<ForeName>Laurent</ForeName>
<Initials>L</Initials>
<AffiliationInfo><Affiliation>Stem Cell laboratory for CNS Disease Modeling, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, Lund, Sweden.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Strategic Research Area MultiPark and Lund Stem Cell Center, Lund University, Lund, Sweden.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Pezzoli</LastName>
<ForeName>Gianni</ForeName>
<Initials>G</Initials>
<AffiliationInfo><Affiliation>Parkinson Institute, ASST G. Pini-CTO, ex ICP, Milano, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Grandori</LastName>
<ForeName>Rita</ForeName>
<Initials>R</Initials>
<AffiliationInfo><Affiliation>Dept. Biotecnology and Biosciences, Università degli Studi di Milano-Bicocca, Milano, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Arnal</LastName>
<ForeName>Isabelle</ForeName>
<Initials>I</Initials>
<AffiliationInfo><Affiliation>Grenoble Institut des Neurosciences, Grenoble, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Cappelletti</LastName>
<ForeName>Graziella</ForeName>
<Initials>G</Initials>
<AffiliationInfo><Affiliation>Dept. Biosciences, Università degli Studi di Milano, Milano, Italy.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Center of Excellence on Neurodegenerative Diseases, Università degli Studi di Milano, Milano, Italy.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2016</Year>
<Month>09</Month>
<Day>15</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>England</Country>
<MedlineTA>Sci Rep</MedlineTA>
<NlmUniqueID>101563288</NlmUniqueID>
<ISSNLinking>2045-2322</ISSNLinking>
</MedlineJournalInfo>
<CitationSubset>IM</CitationSubset>
</MedlineCitation>
<PubmedData><History><PubMedPubDate PubStatus="received"><Year>2016</Year>
<Month>04</Month>
<Day>18</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted"><Year>2016</Year>
<Month>08</Month>
<Day>23</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez"><Year>2016</Year>
<Month>9</Month>
<Day>16</Day>
<Hour>6</Hour>
<Minute>0</Minute>
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<PubMedPubDate PubStatus="pubmed"><Year>2016</Year>
<Month>9</Month>
<Day>16</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="medline"><Year>2016</Year>
<Month>9</Month>
<Day>16</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
</History>
<PublicationStatus>epublish</PublicationStatus>
<ArticleIdList><ArticleId IdType="pubmed">27628239</ArticleId>
<ArticleId IdType="pii">srep33289</ArticleId>
<ArticleId IdType="doi">10.1038/srep33289</ArticleId>
<ArticleId IdType="pmc">PMC5024109</ArticleId>
</ArticleIdList>
</PubmedData>
</pubmed>
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