Differential effect of three-repeat and four-repeat tau on mitochondrial axonal transport

Will Stoothoff, Phillip B Jones, Tara L Spires-Jones, Daniel Joyner, Ekta Chhabra, Kathryn Bercury, Zhanyun Fan, Hong Xie, Brian Bacskai, Jon Edd, Daniel Irimia, Bradley T Hyman

Research output: Contribution to journalArticlepeer-review

Abstract

Tau protein is present in six different splice forms in the human brain and interacts with microtubules via either 3 or 4 microtubule binding repeats. An increased ratio of 3 repeat to 4 repeat isoforms is associated with neurodegeneration in inherited forms of frontotemporal dementia. Tau over-expression diminishes axonal transport in several systems, but differential effects of 3 repeat and 4 repeat isoforms have not been studied. We examined the effects of tau on mitochondrial transport and found that both 3 repeat and 4 repeat tau change normal mitochondrial distribution within the cell body and reduce mitochondrial localization to axons; 4 repeat tau has a greater effect than 3 repeat tau. Further, we observed that the 3 repeat and 4 repeat tau cause different alterations in retrograde and anterograde transport dynamics with 3 repeat tau having a slightly stronger effect on axon transport dynamics. Our results indicate that tau-induced changes in axonal transport may be an underlying theme in neurodegenerative diseases associated with isoform specific changes in tau's interaction with microtubules.
Original languageEnglish
Pages (from-to)417-27
Number of pages11
JournalJournal of Neurochemistry
Volume111
Issue number2
DOIs
Publication statusPublished - Oct 2009

Keywords

  • Animals
  • Axonal Transport
  • Cell Line, Tumor
  • Cerebral Cortex
  • Glioma
  • Green Fluorescent Proteins
  • Humans
  • Mice
  • Microfluidic Analytical Techniques
  • Mitochondria
  • Neurons
  • Protein Transport
  • Repetitive Sequences, Nucleic Acid
  • Tauopathies
  • Transfection
  • tau Proteins

Fingerprint

Dive into the research topics of 'Differential effect of three-repeat and four-repeat tau on mitochondrial axonal transport'. Together they form a unique fingerprint.

Cite this