Local inhibition of microtubule dynamics by dynein is required for neuronal cargo distribution

Nat Commun. 2017 Apr 13;8:15063. doi: 10.1038/ncomms15063.

Abstract

Abnormal axonal transport is associated with neuronal disease. We identified a role for DHC-1, the C. elegans dynein heavy chain, in maintaining neuronal cargo distribution. Surprisingly, this does not involve dynein's role as a retrograde motor in cargo transport, hinging instead on its ability to inhibit microtubule (MT) dynamics. Neuronal MTs are highly static, yet the mechanisms and functional significance of this property are not well understood. In disease-mimicking dhc-1 alleles, excessive MT growth and collapse occur at the dendrite tip, resulting in the formation of aberrant MT loops. These unstable MTs act as cargo traps, leading to ectopic accumulations of cargo and reduced availability of cargo at normal locations. Our data suggest that an anchored dynein pool interacts with plus-end-out MTs to stabilize MTs and allow efficient retrograde transport. These results identify functional significance for neuronal MT stability and suggest a mechanism for cellular dysfunction in dynein-linked disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Axonal Transport
  • COS Cells
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Chlorocebus aethiops
  • Cytoplasmic Dyneins / genetics
  • Cytoplasmic Dyneins / metabolism*
  • Dendrites / metabolism
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Microscopy, Confocal
  • Microtubules / metabolism*
  • Mutation
  • Neurons / metabolism*
  • Time-Lapse Imaging / methods

Substances

  • Caenorhabditis elegans Proteins
  • Green Fluorescent Proteins
  • Cytoplasmic Dyneins
  • DHC-1 protein, C elegans