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α-Synuclein is a Novel Microtubule Dynamase

Cartelli, Daniele ; Aliverti, Alessandro ; Barbiroli, Alberto ; Santambrogio, Carlo ; Ragg, Enzio M. ; Casagrande, Francesca V M ; Cantele, Francesca ; Beltramone, Silvia ; Marangon, Jacopo and De Gregorio, Carmelita , et al. (2016) In Scientific Reports 6.
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... (More)

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.

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publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
6
article number
33289
publisher
Nature Publishing Group
external identifiers
  • scopus:84987888559
  • pmid:27628239
  • wos:000383166600001
ISSN
2045-2322
DOI
10.1038/srep33289
language
English
LU publication?
yes
id
058b5084-ead6-4750-a2e3-be449ac675b7
date added to LUP
2016-11-04 09:36:54
date last changed
2024-04-05 09:22:26
@article{058b5084-ead6-4750-a2e3-be449ac675b7,
  abstract     = {{<p>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 α<sub>2</sub>β<sub>2</sub> 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.</p>}},
  author       = {{Cartelli, Daniele and Aliverti, Alessandro and Barbiroli, Alberto and Santambrogio, Carlo and Ragg, Enzio M. and Casagrande, Francesca V M and Cantele, Francesca and Beltramone, Silvia and Marangon, Jacopo and De Gregorio, Carmelita and Pandini, Vittorio and Emanuele, Marco and Chieregatti, Evelina and Pieraccini, Stefano and Holmqvist, Staffan and Bubacco, Luigi and Roybon, Laurent and Pezzoli, Gianni and Grandori, Rita and Arnal, Isabelle and Cappelletti, Graziella}},
  issn         = {{2045-2322}},
  language     = {{eng}},
  month        = {{09}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{α-Synuclein is a Novel Microtubule Dynamase}},
  url          = {{http://dx.doi.org/10.1038/srep33289}},
  doi          = {{10.1038/srep33289}},
  volume       = {{6}},
  year         = {{2016}},
}