Alpha-Synuclein Is A Novel Microtubule Dynamase

alpha-Synuclein is a presynaptic protein associated to Parkinson's disease, which is unstructured when free in the cytoplasm and adopts a helical conformation when bound to vesicles. After decades of intense studies, alpha-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 alpha-Synuclein and microtubules, which potentially impacts on synaptic functionality. In order to identify the mechanisms underlying these actions, we investigated the interaction between purified alpha-Synuclein and tubulin. We demonstrated that alpha-Synuclein binds to microtubules and tubulin alpha(2)beta(2) tetramer; the latter interaction inducing the formation of helical segment(s) in the alpha-Synuclein polypeptide. This structural change seems to enable alpha-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 alpha-Synuclein variants do not undergo tubulin-induced folding and cause tubulin aggregation rather than polymerization. Our data enable us to propose alpha-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.