Details

Autor(en) / Beteiligte

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

Titel

α-Synuclein is a Novel Microtubule Dynamase

Ist Teil von

• Scientific reports, 2016-09, Vol.6 (1), p.33289-33289, Article 33289

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2016

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.