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dSarm/Sarm1 Is Required for Activation of an Injury-Induced Axon Death Pathway
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dSarm/Sarm1 Is Required for Activation of an Injury-Induced Axon Death Pathway
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Journal Article
dSarm/Sarm1 Is Required for Activation of an Injury-Induced Axon Death Pathway
2012
Overview
Axonal and synaptic degeneration is a hallmark of peripheral neuropathy, brain injury, and neurodegenerative disease. Axonal degeneration has been proposed to be mediated by an active autodestruction program, akin to apoptotic cell death; however, loss-of-function mutations capable of potently blocking axon self-destruction have not been described. Here, we show that loss of the Drosophila Toll receptor adaptor dSarm (sterile α/Armadillo/Toll-Interleukin receptor homology domain protein) cell-autonomously suppresses Wallerian degeneration for weeks after axotomy. Severed mouse Sarm1 null axons exhibit remarkable long-term survival both in vivo and in vitro, indicating that Sarm1 prodegenerative signaling is conserved in mammals. Our results provide direct evidence that axons actively promote their own destruction after injury and identify dSarm/Sarm1 as a member of an ancient axon death signaling pathway.
Publisher
American Association for the Advancement of Science,The American Association for the Advancement of Science
Subject
/ Animals
/ Animals, Genetically Modified
/ Armadillo Domain Proteins - analysis
/ Armadillo Domain Proteins - genetics
/ Armadillo Domain Proteins - physiology
/ Axons
/ Axotomy
/ Biological and medical sciences
/ Cranial nerves. Spinal roots. Peripheral nerves. Autonomic nervous system. Gustation. Olfaction
/ Cytoskeletal Proteins - analysis
/ Cytoskeletal Proteins - genetics
/ Cytoskeletal Proteins - physiology
/ Drosophila Proteins - analysis
/ Drosophila Proteins - genetics
/ Drosophila Proteins - physiology
/ Embryos
/ Fundamental and applied biological sciences. Psychology
/ Injuries
/ Mice
/ Mutation
/ Nerves
/ Nervous system (semeiology, syndromes)
/ Neurons
/ Rodents
/ Superior Cervical Ganglion - cytology
/ Survival
