Axon injury and stress trigger a microtubule-based neuroprotective pathway.
Axon injury elicits profound cellular changes, including axon regeneration. However, the full range of neuronal injury responses remains to be elucidated. Surprisingly, after axons of Drosophila dendritic arborization neurons were severed, dendrites were more resistant to injury-induced degeneration. Concomitant with stabilization, microtubule dynamics in dendrites increased. Moreover, dendrite stabilization was suppressed when microtubule dynamics was dampened, which was achieved by lowering levels of the microtubule nucleation protein γ-tubulin. Increased microtubule dynamics and global neuronal stabilization were also activated by expression of expanded polyglutamine (poly-Q) proteins SCA1, SCA3, and huntingtin. In all cases, dynamics were increased through microtubule nucleation and depended on JNK signaling, indicating that acute axon injury and long-term neuronal stress activate a common cytoskeleton-based stabilization program. Reducing levels of γ-tubulin exacerbated long-term degeneration induced by SCA3 in branched sensory neurons and in a well established Drosophila eye model of poly-Q-induced neurodegeneration. Thus, increased microtubule dynamics can delay short-term injury-induced degeneration, and, in the case of poly-Q proteins, can counteract progressive longer-term degeneration. We conclude that axon injury or stress triggers a microtubule-based neuroprotective pathway that stabilizes neurons against degeneration.
Department of Biochemistry and Molecular Biology, Penn State University, University Park, PA 16802, USA.
Li
L
Chen
Michelle C
MC
Stone
Juan
J
Tao
Melissa M
MM
Rolls
D000818:Animals; D001369:Axons / Q000473:pathology / Q000502:physiology*; D003712:Dendrites / Q000502:physiology / Q000648:ultrastructure; D004330:Drosophila; D008870:Microtubules / Q000502:physiology*; D009416:Nerve Regeneration / Q000502:physiology*; D010455:Peptides / Q000378:metabolism; D059348:Peripheral Nerve Injuries / Q000503:physiopathology*; D034622:RNA Interference; D013312:Stress, Physiological / Q000502:physiology*; D059008:Time-Lapse Imaging
D010455:Peptides; C097188:polyglutamine