Dynein- and activity-dependent retrograde transport of autophagosomes in neuronal axons

Kiyoshi Katsumata, Jun Nishiyama, Takafumi Inoue, Noboru Mizushima, Junzo Takeda, Michisuke Yuzaki

Research output: Contribution to journalReview article

44 Citations (Scopus)

Abstract

The accumulation of autophagosomes within axons is often observed in axonopathies associated with various neurological disorders, including those following excitotoxic insults. Nevertheless, the life cycle of autophagosomes in axons is not well understood. In the present study, we used microexplant cultures of cerebellar granule cells from GFP-LC3 transgenic mice to perform time-lapse imaging of LC3-positive dots in identified axons. Since these GFP-LC3 dots were never observed in granule cells on an Atg5-null background, they were considered to represent autophagosomes. Under physiological conditions, the autophagosomes showed bidirectional and saltatory movement with a bias towards one direction. Such vectorial movement was largely blocked by the dynein motor inhibitor EHNA (erythro-9-[3-(2-hydroxynonyl)] adenine), suggesting that the autophagosomes moved towards the soma, where most lysosomes are located. Interestingly, the application of the glutamate analog N-methyl-D-aspartic acid (NMDA) as an excitotoxin increased the number of autophagosomes in axons, while it did not significantly change its movement characteristics. These results suggest that autophagosomes play important roles in axons and are dynamically regulated under physiological and pathological conditions.

Original languageEnglish
Pages (from-to)378-385
Number of pages8
JournalAutophagy
Volume6
Issue number3
DOIs
Publication statusPublished - 2010 Apr 1

Keywords

  • Autophagosome
  • Cerebellum
  • EHNA
  • Granule cell
  • Imaging
  • NMDA

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Katsumata, K., Nishiyama, J., Inoue, T., Mizushima, N., Takeda, J., & Yuzaki, M. (2010). Dynein- and activity-dependent retrograde transport of autophagosomes in neuronal axons. Autophagy, 6(3), 378-385. https://doi.org/10.4161/auto.6.3.11262