Spastin, atlastin, and ER relocalization are involved in axon but not dendrite regeneration.
Mutations in >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.
Biochemistry and Molecular Biology and Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA 16802.
Kavitha
K
Rao
Biochemistry and Molecular Biology and Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA 16802.
Michelle C
MC
Stone
Biochemistry and Molecular Biology and Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA 16802.|Molecular, Cellular and Integrative Biosciences Graduate Program, Pennsylvania State University, University Park, PA 16802.
Alexis T
AT
Weiner
Biochemistry and Molecular Biology and Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA 16802.|Molecular, Cellular and Integrative Biosciences Graduate Program, Pennsylvania State University, University Park, PA 16802.
Kyle W
KW
Gheres
Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261.
Chaoming
C
Zhou
Neurobiology and Behavior, Cornell University, Ithaca, NY 14853.
David L
DL
Deitcher
Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261.
Edwin S
ES
Levitan
Biochemistry and Molecular Biology and Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA 16802 mur22@psu.edu.|Molecular, Cellular and Integrative Biosciences Graduate Program, Pennsylvania State University, University Park, PA 16802.
Melissa M
MM
Rolls
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000502:physiology; D003712:Dendrites / Q000378:metabolism / Q000502:physiology; D004330:Drosophila / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000502:physiology; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D008870:Microtubules; D008928:Mitochondria / Q000378:metabolism; D009154:Mutation; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology; D034622:RNA Interference; D012038:Regeneration / Q000502:physiology*; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics / Q000378:metabolism
D029721:Drosophila Proteins; D008565:Membrane Proteins; C518508:spict protein, Drosophila; D000251:Adenosine Triphosphatases; D020558:GTP Phosphohydrolases; C543694:atl protein, Drosophila; C501874:spas protein, Drosophila