Caenorhabditis elegansF-Box Protein Promotes Axon Regeneration by Inducing Degradation of the Mad Transcription Factor
Autor: | Hiroshi Hanafusa, Yoshiki Sakai, Naoki Hisamoto, Strahil Iv. Pastuhov, Yasuko Todoroki, Tatsuhiro Shimizu, Kunihiro Matsumoto |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
F-box protein Receptor tyrosine kinase 03 medical and health sciences 0302 clinical medicine Mad/Max ubiquitin Gene expression medicine Axon Transcription factor Research Articles Caenorhabditis elegans biology Chemistry General Neuroscience Regeneration (biology) axon regeneration biology.organism_classification Cell biology 030104 developmental biology medicine.anatomical_structure nervous system Proteasome C. elegans biology.protein 030217 neurology & neurosurgery Cellular/Molecular |
Zdroj: | The Journal of Neuroscience |
ISSN: | 1529-2401 0270-6474 |
DOI: | 10.1523/jneurosci.1024-20.2021 |
Popis: | In Caenorhabditis elegans, axon regeneration is activated by a signaling cascade through the receptor tyrosine kinase (RTK) SVH-2. Axonal injury induces svh-2 gene expression by degradation of the Mad-like transcription factor MDL-1. In this study, we identify the svh-24/sdz-33 gene encoding a protein containing F-box and F-box-associated domains as a regulator of axon regeneration in motor neurons. We find that sdz-33 is required for axon injury-induced svh-2 expression. In Caenorhabditis elegans, axon regeneration is activated by a signaling cascade through the receptor tyrosine kinase (RTK) SVH-2. Axonal injury induces svh-2 gene expression by degradation of the Mad-like transcription factor MDL-1. In this study, we identify the svh-24/sdz-33 gene encoding a protein containing F-box and F-box-associated domains as a regulator of axon regeneration in motor neurons. We find that sdz-33 is required for axon injury-induced svh-2 expression. SDZ-33 targets MDL-1 for poly-ubiquitylation and degradation. Furthermore, we demonstrate that SDZ-33 promotes axotomy-induced nuclear degradation of MDL-1, resulting in the activation of svh-2 expression in animals. These results suggest that the F-box protein is required for RTK signaling in the control of axon regeneration. SIGNIFICANCE STATEMENT In Caenorhabditis elegans, axon regeneration is positively regulated by the growth factor SVH-1 and its receptor tyrosine kinase SVH-2. Expression of the svh-2 gene is induced by axonal injury via the Ets-like transcription factor ETS-4, whose transcriptional activity is inhibited by the Mad-like transcription factor MDL-1. Axon injury leads to the degradation of MDL-1, and this is linked to the activation of ETS-4 transcriptional activity. In this study, we identify the sdz-33 gene encoding a protein containing an F-box domain as a regulator of axon regeneration. We demonstrate that MDL-1 is poly-ubiquitylated and degraded through the SDZ-33-mediated 26S proteasome pathway. These results reveal that an F-box protein promotes axon regeneration by degrading the Mad transcription factor. |
Databáze: | OpenAIRE |
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