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.
Cartelli, D., Aliverti, A., Barbiroli, A., SANTAMBROGIO, C., Ragg, E., Casagrande, F., et al. (2016). α-Synuclein is a Novel Microtubule Dynamase. SCIENTIFIC REPORTS, 6, 1-13 [10.1038/srep33289].
Citazione: | Cartelli, D., Aliverti, A., Barbiroli, A., SANTAMBROGIO, C., Ragg, E., Casagrande, F., et al. (2016). α-Synuclein is a Novel Microtubule Dynamase. SCIENTIFIC REPORTS, 6, 1-13 [10.1038/srep33289]. | |
Tipo: | Articolo in rivista - Articolo scientifico | |
Carattere della pubblicazione: | Scientifica | |
Presenza di un coautore afferente ad Istituzioni straniere: | Si | |
Titolo: | α-Synuclein is a Novel Microtubule Dynamase | |
Autori: | Cartelli, D; Aliverti, A; Barbiroli, A; SANTAMBROGIO, C; Ragg, E; Casagrande, F; Cantele, F; Beltramone, S; Marangon, J; De Gregorio, C; Pandini, V; Emanuele, M; Chieregatti, E; Pieraccini, S; Holmqvist, S; Bubacco, L; Roybon, L; Pezzoli, G; GRANDORI, R; Arnal, I; Cappelletti, G | |
Autori: | ||
Data di pubblicazione: | 2016 | |
Lingua: | English | |
Rivista: | SCIENTIFIC REPORTS | |
Digital Object Identifier (DOI): | http://dx.doi.org/10.1038/srep33289 | |
Appare nelle tipologie: | 01 - Articolo su rivista |
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