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Expanding the Toolkit for In Vivo Imaging of Axonal Transport
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Alpha-synuclein facilitates to form short unconventional microtubules that have a unique function in the axonal

Shiori Toba1, Mingyue Jin1, Masami Yamada1

  • 1Department of Genetic Disease Research, Osaka City University Graduate School of Medicine, Asahi-machi 1-4-3 Abeno, Osaka, 545-8585, Japan.

Scientific Reports
|November 29, 2017
PubMed

Insights

Alpha-synuclein (αSyn) facilitates the formation of short, mobile microtubules crucial for axonal transport. This discovery offers new insights into the pathogenesis of Parkinson's disease (PD).

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • Alpha-synuclein (αSyn) is implicated in Parkinson's disease (PD), but its precise role remains unclear.
  • Previous models proposed transportable microtubules (tMTs) involving dynein and kinesin, but tMT formation mechanisms were unknown.

Purpose of the Study:

  • To investigate the role of αSyn in microtubule dynamics and axonal transport.
  • To elucidate the mechanisms underlying the formation of transportable microtubules.

Main Methods:

  • In vitro microtubule dynamics assays.
  • Live-cell imaging and co-transport analysis.
  • Super-resolution microscopy (SR-PALM) and nerve tissue analysis.

Main Results:

  • αSyn promotes the formation of short microtubules, preferentially binding to 14-protofilament (14-pfs) microtubules.
  • αSyn co-transports with dynein and βIII-tubulin fragments in anterograde transport.
  • Depletion of αSyn and γSyn impairs bi-directional axonal transport; 14-pfs microtubules are mobile and increase upon nerve injury.

Conclusions:

  • αSyn facilitates the formation of short, mobile tMTs essential for axonal transport.
  • This study reveals a novel mechanism linking αSyn to axonal transport dysfunction in PD pathogenesis.

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