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dc.contributor.advisorGabel, Christopher V.en_US
dc.contributor.authorTaub, Daniel Garrisonen_US
dc.date.accessioned2019-04-12T14:35:59Z
dc.date.issued2019
dc.identifier.urihttps://hdl.handle.net/2144/34794
dc.description.abstractAxonal regeneration within the mammalian central nervous system following traumatic damage is limited and interventions to enable regrowth is a crucial goal in regenerative medicine. The nematode Caenorhabditis elegans is an excellent model to identify the intrinsic genetic programs that govern axonal regrowth. Here we demonstrate that alterations in O-linked N- beta-acetylglucosamine (O-GlcNAc) post-translational modifications of proteins can increase the regenerative potential of individual neurons. O-GlcNAc are single monosaccharide protein modifications that occur on serines/threonines in nucleocytoplasmic compartments. Changes in O-GlcNAc levels serve as a sensor of cellular nutrients and acts in part through the insulin-signaling pathway. Loss of O-GlcNAc via mutation of the O-GlcNAc Transferase (OGT), the enzyme that adds O-GlcNAc onto target proteins, enhances regeneration by 70%. Remarkably, hyper-O-GlcNAcyation via mutation of the O-GlcNAcase (OGA), the enzyme that removes O-GlcNAc from target proteins, also enhances regeneration by 40%. Our results shed light on this apparent contradiction by demonstrating that O-GlcNAc enzyme mutants differentially modulate the insulin-signaling pathway. OGT mutants act through AKT1 to modulate glycolysis. In contrast, OGA mutants act through the FOXO/DAF-16 transcription factor to improve the mitochondrial stress response. These findings reveal for the first time the importance of O-GlcNAc post-translational modifications in axon regeneration and provide evidence that regulation of metabolic programs can dictate the regenerative capacity of a neuron.en_US
dc.language.isoen_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internationalen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectNeurosciencesen_US
dc.subjectAxon regenerationen_US
dc.subjectC. elegansen_US
dc.subjectInsulin signalingen_US
dc.subjectMetabolismen_US
dc.subjectO-GlcNAcen_US
dc.titleO-linked beta N-acetylglucosamine (O-GlcNAc) post-translational modifications govern axon regenerationen_US
dc.typeThesis/Dissertationen_US
dc.date.updated2019-02-21T02:02:17Z
dc.description.embargo2021-02-20T00:00:00Z
etd.degree.nameDoctor of Philosophyen_US
etd.degree.leveldoctoralen_US
etd.degree.disciplineBiophysicsen_US
etd.degree.grantorBoston Universityen_US


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Attribution-NonCommercial-NoDerivatives 4.0 International
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivatives 4.0 International