Reference - Detail
| RRC ID | 56858 |
|---|---|
| Author | Hertz NT, Adams EL, Weber RA, Shen RJ, O'Rourke MK, Simon DJ, Zebroski H, Olsen O, Morgan CW, Mileur TR, Hitchcock AM, Sinnott Armstrong NA, Wainberg M, Bassik MC, Molina H, Wells JA, Tessier-Lavigne M. |
| Title | Neuronally Enriched RUFY3 Is Required for Caspase-Mediated Axon Degeneration. |
| Journal | Neuron |
| Abstract |
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. |
| Volume | 103(3) |
| Pages | 412-422.e4 |
| Published | 2019-8-7 |
| DOI | 10.1016/j.neuron.2019.05.030 |
| PII | S0896-6273(19)30483-0 |
| PMID | 31221560 |
| PMC | PMC8024238 |
| MeSH | Animals Axons / enzymology Axons / pathology* Caspase 3 / physiology Cells, Cultured Cytoskeletal Proteins Enzyme Activation Ganglia, Spinal / cytology Ganglia, Spinal / embryology Mice Mice, Knockout Nerve Degeneration / enzymology Nerve Degeneration / pathology* Nerve Tissue Proteins / chemistry Nerve Tissue Proteins / deficiency Nerve Tissue Proteins / physiology* Phosphorylation Protein Processing, Post-Translational Receptor, trkA / physiology Sensory Receptor Cells / physiology Structure-Activity Relationship |
| IF | 14.403 |
| Times Cited | 1 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 14 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Mice | RBRC05780 |