Neuronally-enriched RUFY3 is Required for Caspase-Mediated Axon Degeneration
| Autor: | Charles W. Morgan, Melanie K. O’Rourke, David J. Simon, Nicholas Sinnott Armstrong, Michael C. Bassik, Rebecca J. Shen, Olav Olsen, Trevor R. Mileur, Henry Zebroski, Ross A. Weber, Michael Wainberg, James A. Wells, Angela M. Hitchcock, Marc Tessier-Lavigne, Henrik Molina, Eliza L. Adams, Nicholas T. Hertz |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Sensory Receptor Cells Chemical biology Endogeny Sensory system Nerve Tissue Proteins Degeneration (medical) Tropomyosin receptor kinase A Article Dephosphorylation 03 medical and health sciences Mice Structure-Activity Relationship 0302 clinical medicine Ganglia Spinal medicine Animals Phosphorylation Receptor trkA Caspase Cells Cultured Mice Knockout biology Chemistry Caspase 3 General Neuroscience Neurodegeneration medicine.disease Axons Cell biology Enzyme Activation Cytoskeletal Proteins 030104 developmental biology nervous system Nerve Degeneration biology.protein Protein Processing Post-Translational 030217 neurology & neurosurgery |
| Zdroj: | Neuron |
| Popis: | Summary Selective synaptic and axonal degeneration are critical aspects of both brain development and neurodegenerative disease. Inhibition of caspase signaling in neurons is a potential therapeutic strategy for neurodegenerative disease, but no neuron-specific modulators of caspase signaling have been described. Using a mass spectrometry approach, we discovered that RUFY3, a neuronally enriched protein, is essential for caspase-mediated degeneration of TRKA+ sensory axons in vitro and in vivo. Deletion of Rufy3 protects axons from degeneration, even in the presence of activated CASP3 that is competent to cleave endogenous substrates. Dephosphorylation of RUFY3 at residue S34 appears required for axon degeneration, providing a potential mechanism for neurons to locally control caspase-driven degeneration. Neuronally enriched RUFY3 thus provides an entry point for understanding non-apoptotic functions of CASP3 and a potential target to modulate caspase signaling specifically in neurons for neurodegenerative disease. |
| Databáze: | OpenAIRE |
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