Spastin and Atlastin mechanism investigated
This study of HSP proteins in fruit flies demonstrates that spastin and atlastin promote axon regeneration by coordinating concentration of the endoplasmic reticulum and microtubules at the growing axon tip.
Mutations in more than 50 genes, including spastin and atlastin, lead to hereditary spastic paraplegia (HSP). We previously demonstrated that reduction of spastin leads to a deficit 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.
SOURCE: Mol Biol Cell. 2016 Nov 1;27(21):3245-3256. Epub 2016 Sep 7. © 2016 Rao et al. PMID: 27605706 DOI: 10.1091/mbc.E16-05-0287
Spastin, atlastin, and ER relocalization are involved in axon but not dendrite regeneration.
Rao K1, Stone MC1, Weiner AT1,2, Gheres KW1,2, Zhou C3, Deitcher DL4, Levitan ES3, Rolls MM5,2.
1 Biochemistry and Molecular Biology and Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA 16802.
2 Molecular, Cellular and Integrative Biosciences Graduate Program, Pennsylvania State University, University Park, PA 16802.
3 Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261.
4 Neurobiology and Behavior, Cornell University, Ithaca, NY 14853.
5 Biochemistry and Molecular Biology and Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA 16802 [email protected]