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α-Synuclein is a No...
α-Synuclein is a Novel Microtubule Dynamase
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- Cartelli, Daniele (author)
- University of Milan
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- Aliverti, Alessandro (author)
- University of Milan
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- Barbiroli, Alberto (author)
- University of Milan
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- Santambrogio, Carlo (author)
- University of Milano-Bicocca
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- Ragg, Enzio M. (author)
- University of Milan
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- Casagrande, Francesca V M (author)
- University of Milan
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- Cantele, Francesca (author)
- University of Milan
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- Beltramone, Silvia (author)
- University of Milan
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- Marangon, Jacopo (author)
- University of Milan
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- De Gregorio, Carmelita (author)
- University of Milan
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- Pandini, Vittorio (author)
- University of Milan
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- Emanuele, Marco (author)
- Italian Institute of Technology
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- Chieregatti, Evelina (author)
- Italian Institute of Technology
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- Pieraccini, Stefano (author)
- University of Milan
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- Holmqvist, Staffan (author)
- Lund University,Lunds universitet,Stamcellslaboratoriet för sjukdomsmodellering i det centrala nervsystemet,Forskargrupper vid Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,IPSC Laboratory for CNS Disease Modeling,Lund University Research Groups,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine
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- Bubacco, Luigi (author)
- University of Padova
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- Roybon, Laurent (author)
- Lund University,Lunds universitet,Stamcellslaboratoriet för sjukdomsmodellering i det centrala nervsystemet,Forskargrupper vid Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,IPSC Laboratory for CNS Disease Modeling,Lund University Research Groups,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine
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- Pezzoli, Gianni (author)
- Istituti Clinici Di Perfezionamento Hospital , Milan
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- Grandori, Rita (author)
- University of Milano-Bicocca
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- Arnal, Isabelle (author)
- Grenoble Institute of Neurosciences
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- Cappelletti, Graziella (author)
- University of Milan
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(creator_code:org_t)
- 2016-09-15
- 2016
- English.
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
- Related links:
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http://dx.doi.org/10... (free)
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https://www.nature.c...
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https://doi.org/10.1...
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
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Cartelli, Daniel ...
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Aliverti, Alessa ...
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Barbiroli, Alber ...
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Santambrogio, Ca ...
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Ragg, Enzio M.
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Casagrande, Fran ...
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Cantele, Frances ...
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Beltramone, Silv ...
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Marangon, Jacopo
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De Gregorio, Car ...
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Pandini, Vittori ...
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Emanuele, Marco
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Chieregatti, Eve ...
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Pieraccini, Stef ...
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Holmqvist, Staff ...
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Bubacco, Luigi
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Roybon, Laurent
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Pezzoli, Gianni
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Grandori, Rita
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Arnal, Isabelle
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Cappelletti, Gra ...
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