α-Synuclein is a Novel Microtubule Dynamase

Research output: Contribution to journalArticle

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 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.

Details

Authors
  • Daniele Cartelli
  • Alessandro Aliverti
  • Alberto Barbiroli
  • Carlo Santambrogio
  • Enzio M. Ragg
  • Francesca V M Casagrande
  • Francesca Cantele
  • Silvia Beltramone
  • Jacopo Marangon
  • Carmelita De Gregorio
  • Vittorio Pandini
  • Marco Emanuele
  • Evelina Chieregatti
  • Stefano Pieraccini
  • Staffan Holmqvist
  • Luigi Bubacco
  • Gianni Pezzoli
  • Rita Grandori
  • Isabelle Arnal
  • Graziella Cappelletti
Organisations
External organisations
  • Italian Institute of Technology
  • University of Padova
  • University of Milano-Bicocca
  • University of Milan
  • Grenoble Institute of Neurosciences
  • Istituti Clinici di Perfezionamento (ICP)
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurology
  • Cell and Molecular Biology
Original languageEnglish
Article number33289
JournalScientific Reports
Volume6
Publication statusPublished - 2016 Sep 15
Publication categoryResearch
Peer-reviewedYes