Journal
CELL REPORTS
Volume 2, Issue 5, Pages 1340-1350Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2012.09.032
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Funding
- Spastic Paraplegia Foundation
- National Institute of Neurological Disorders and Stroke [R21 NS066216, R01 NS63896]
- National Institute of General Medical Sciences [R01 GM085115]
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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.
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