Normal Spastin Gene Dosage Is Specifically Required for Axon Regeneration

Cell Rep. 2012 Nov 29;2(5):1340-50. doi: 10.1016/j.celrep.2012.09.032. Epub 2012 Nov 1.

Abstract

Axon regeneration allows neurons to repair circuits after trauma; however, most of the molecular players in this process remain to be identified. Given that microtubule rearrangements have been observed in injured neurons, we tested whether microtubule-severing proteins might play a role in axon regeneration. We found that axon regeneration is extremely sensitive to levels of the microtubule-severing protein spastin. Although microtubule behavior in uninjured neurons was not perturbed in animals heterozygous for a spastin null allele, axon regeneration was severely disrupted in this background. Two types of axon regeneration-regeneration of an axon from a dendrite after proximal axotomy and regeneration of an axon from the stump after distal axotomy-were defective in Drosophila with one mutant copy of the spastin gene. Other types of axon and dendrite outgrowth, including regrowth of dendrites after pruning, were normal in heterozygotes. We conclude that regenerative axon growth is uniquely sensitive to spastin gene dosage.

Publication types

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

MeSH terms

  • Adenosine Triphosphatases / antagonists & inhibitors
  • Adenosine Triphosphatases / genetics*
  • Adenosine Triphosphatases / metabolism
  • Alleles
  • Animals
  • Axons / metabolism*
  • Dendrites / metabolism
  • Drosophila / metabolism
  • Drosophila Proteins / antagonists & inhibitors
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism
  • Gene Dosage
  • Katanin
  • Microtubules / metabolism
  • Mutation
  • Nerve Regeneration / physiology*
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Tubulin / chemistry
  • Tubulin / genetics
  • Tubulin / metabolism

Substances

  • Drosophila Proteins
  • RNA, Small Interfering
  • Tubulin
  • Adenosine Triphosphatases
  • spas protein, Drosophila
  • Kat-60L1 protein, Drosophila
  • Katanin