TIR-1/SARM1 inhibits axon regeneration and promotes axon degeneration
Student AuthorsVictoria Julian Czech
UMass Chan AffiliationsNeurobiology
Document TypeJournal Article
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AbstractGrowth and destruction are central components of the neuronal injury response. Injured axons that are capable of repair, including axons in the mammalian peripheral nervous system and in many invertebrate animals, often regenerate and degenerate on either side of the injury. Here we show that TIR-1/dSarm/SARM1, a key regulator of axon degeneration, also inhibits regeneration of injured motor axons. The increased regeneration in tir-1 mutants is not a secondary consequence of its effects on degeneration, nor is it determined by the NADase activity of TIR-1. Rather, we found that TIR-1 functions cell-autonomously to regulate each of the seemingly opposite processes through distinct interactions with two MAP kinase pathways. On one side of the injury, TIR-1 inhibits axon regeneration by activating the NSY-1/ASK1 MAPK signaling cascade, while on the other side of the injury, TIR-1 simultaneously promotes axon degeneration by interacting with the DLK-1 mitogen-activated protein kinase (MAPK) signaling cascade. In parallel, we found that the ability to cell-intrinsically inhibit axon regeneration is conserved in human SARM1. Our finding that TIR-1/SARM1 regulates axon regeneration provides critical insight into how axons coordinate a multidimensional response to injury, consequently informing approaches to manipulate the response toward repair.
SourceCzech VL, O'Connor LC, Philippon B, Norman E, Byrne AB. TIR-1/SARM1 inhibits axon regeneration and promotes axon degeneration. Elife. 2023 Apr 21;12:e80856. doi: 10.7554/eLife.80856. PMID: 37083456; PMCID: PMC10121217.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/52027
RightsCopyright Czech, O'Connor et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.; Attribution 4.0 International
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Except where otherwise noted, this item's license is described as Copyright Czech, O'Connor et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.