Spastin, atlastin, and ER relocalization are involved in axon but not dendrite regeneration

Kavitha Rao, Michelle C. Stone, Alexis T. Weiner, Kyle W. Gheres, Chaoming Zhou, David L. Deitcher, Edwin S. Levitan, Melissa M. Rolls

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Mutations in >50 genes, including spastin and atlastin, lead to hereditary spastic paraplegia (HSP). We previously demonstrated that reduction of spastin leads to a defcit in axon regeneration in a Drosophila model. Axon regeneration was similarly impaired in neurons when HSP proteins atlastin, seipin, and spichthyin were reduced. Impaired regeneration was dependent on genetic background and was observed when partial reduction of HSP proteins was combined with expression of dominant-negative microtubule regulators, suggesting that HSP proteins work with microtubules to promote regeneration. Microtubule rearrangements triggered by axon injury were, however, normal in all genotypes. We examined other markers to identify additional changes associated with regeneration. Whereas mitochondria, endosomes, and ribosomes did not exhibit dramatic repatterning during regeneration, the endoplasmic reticulum (ER) was frequently concentrated near the tip of the growing axon. In atlastin RNAi and spastin mutant animals, ER accumulation near single growing axon tips was impaired. ER tip concentration was observed only during axon regeneration and not during dendrite regeneration. In addition, dendrite regeneration was unaffected by reduction of spastin or atlastin. We propose that the HSP proteins spastin and atlastin promote axon regeneration by coordinating concentration of the ER and microtubules at the growing axon tip.

Original languageEnglish (US)
Pages (from-to)3245-3256
Number of pages12
JournalMolecular biology of the cell
Volume27
Issue number21
DOIs
StatePublished - Nov 1 2016

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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