Intermediate filament accumulation can stabilize microtubules in Caenorhabditis elegans motor neurons

Proc Natl Acad Sci U S A. 2018 Mar 20;115(12):3114-3119. doi: 10.1073/pnas.1721930115. Epub 2018 Mar 6.

Abstract

Neural circuits utilize a coordinated cellular machinery to form and eliminate synaptic connections, with the neuronal cytoskeleton playing a prominent role. During larval development of Caenorhabditis elegans, synapses of motor neurons are stereotypically rewired through a process facilitated by dynamic microtubules (MTs). Through a genetic suppressor screen on mutant animals that fail to rewire synapses, and in combination with live imaging and ultrastructural studies, we find that intermediate filaments (IFs) stabilize MTs to prevent synapse rewiring. Genetic ablation of IFs or pharmacological disruption of IF networks restores MT growth and rescues synapse rewiring defects in the mutant animals, indicating that IF accumulation directly alters MT stability. Our work sheds light on the impact of IFs on MT dynamics and axonal transport, which is relevant to the mechanistic understanding of several human motor neuron diseases characterized by IF accumulation in axonal swellings.

Keywords: C. elegans; intermediate filaments; microtubules; neurons; synapses.

Publication types

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

MeSH terms

  • Animals
  • Axonal Transport
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / metabolism
  • Cytoskeleton / metabolism
  • Gene Expression Regulation / physiology
  • Intermediate Filament Proteins / genetics
  • Intermediate Filament Proteins / metabolism*
  • Microtubules / physiology*
  • Motor Neurons / cytology
  • Motor Neurons / physiology*
  • Synapses / physiology

Substances

  • Caenorhabditis elegans Proteins
  • Intermediate Filament Proteins