Journal
CELL REPORTS
Volume 24, Issue 8, Pages 1931-+Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2018.07.078
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Funding
- National Institute of Neurological Disorders and Stroke [R01 NS077929]
- Ruth L. Kirschstein National Research Service [F31 NS095464]
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Regrowth of an axon after injury is an inherently metabolic undertaking. Yet the mechanisms of metabolic regulation that influence repair following injury are not well understood. O-linked beta-N-acetylglucos-amine (O-GlcNAc) is a post-translational modification of serines and threonines that functions as a sensor of cellular nutrients. Performing in vivo laser axotomies in Caenorhabditis elegans, we find that neuronal regeneration is substantially increased by disruptions of either the O-GlcNAc transferase or the O-GlcNAcase that decrease and increase O-GlcNAc levels, respectively. A lack of O-GlcNAc induces the AKT-1 branch in the insulin-signaling pathway to use glycolysis. In contrast, increased O-GlcNAc levels activate an opposing branch of the insulin-signaling pathway whereby SGK-1 modulates the FOXO transcription factor DAF-16 to influence mitochondrial function. The existence of this toggle-like mechanism between metabolic pathways suggests that O-GlcNAc signaling conveys cellular nutrient status to orchestrate metabolism in a damaged neuron and maximize the regenerative response.
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