A dominant mutation in mec-7/β-tubulin affects axon development and regeneration in Caenorhabditis elegans neurons

Mol Biol Cell. 2013 Feb;24(3):285-96. doi: 10.1091/mbc.E12-06-0441. Epub 2012 Dec 5.

Abstract

Microtubules have been known for decades to be basic elements of the cytoskeleton. They form long, dynamic, rope-like structures within the cell that are essential for mitosis, maintenance of cell shape, and intracellular transport. More recently, in vitro studies have implicated microtubules as signaling molecules that, through changes in their stability, have the potential to trigger growth of axons and dendrites in developing neurons. In this study, we show that specific mutations in the Caenorhabditis elegans mec-7/β-tubulin gene cause ectopic axon formation in mechanosensory neurons in vivo. In mec-7 mutants, the ALM mechanosensory neuron forms a long ectopic neurite that extends posteriorly, a phenotype that can be mimicked in wild-type worms with a microtubule-stabilizing drug (paclitaxel), and suppressed by mutations in unc-33/CRMP2 and the kinesin-related gene, vab-8. Our results also reveal that these ectopic neurites contain RAB-3, a marker for presynaptic loci, suggesting that they have axon-like properties. Interestingly, in contrast with the excessive axonal growth observed during development, mec-7 mutants are inhibited in axonal regrowth and remodeling following axonal injury. Together our results suggest that MEC-7/β-tubulin integrity is necessary for the correct number of neurites a neuron generates in vivo and for the capacity of an axon to regenerate.

Publication types

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

MeSH terms

  • Animals
  • Caenorhabditis elegans / cytology
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / genetics*
  • Caenorhabditis elegans Proteins / metabolism
  • Colchicine / pharmacology
  • Genes, Dominant
  • Mitogen-Activated Protein Kinases / genetics
  • Mutation
  • Nerve Growth Factors / genetics
  • Nerve Regeneration / genetics*
  • Neurites / drug effects
  • Neurites / physiology*
  • Neurons / drug effects
  • Neurons / physiology
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Protein Transport
  • Sequence Analysis, DNA
  • Synapses / metabolism
  • Tubulin / genetics*
  • Tubulin / metabolism
  • Tubulin Modulators / pharmacology
  • Wnt Proteins / genetics

Substances

  • Caenorhabditis elegans Proteins
  • Mec-7 protein, C elegans
  • Nerve Growth Factors
  • Tubulin
  • Tubulin Modulators
  • Wnt Proteins
  • unc-33 protein, C elegans
  • vab-8 protein, C elegans
  • Mitogen-Activated Protein Kinases
  • Colchicine