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Publication : Neddylation orchestrates the complex transcriptional and posttranscriptional program that drives Schwann cell myelination.

First Author  Ayuso-García P Year  2024
Journal  Sci Adv Volume  10
Issue  15 Pages  eadm7600
PubMed ID  38608019 Mgi Jnum  J:351980
Mgi Id  MGI:7622861 Doi  10.1126/sciadv.adm7600
Citation  Ayuso-Garcia P, et al. (2024) Neddylation orchestrates the complex transcriptional and posttranscriptional program that drives Schwann cell myelination. Sci Adv 10(15):eadm7600
abstractText  Myelination is essential for neuronal function and health. In peripheral nerves, >100 causative mutations have been identified that cause Charcot-Marie-Tooth disease, a disorder that can affect myelin sheaths. Among these, a number of mutations are related to essential targets of the posttranslational modification neddylation, although how these lead to myelin defects is unclear. Here, we demonstrate that inhibiting neddylation leads to a notable absence of peripheral myelin and axonal loss both in developing and regenerating mouse nerves. Our data indicate that neddylation exerts a global influence on the complex transcriptional and posttranscriptional program by simultaneously regulating the expression and function of multiple essential myelination signals, including the master transcription factor EGR2 and the negative regulators c-Jun and Sox2, and inducing global secondary changes in downstream pathways, including the mTOR and YAP/TAZ signaling pathways. This places neddylation as a critical regulator of myelination and delineates the potential pathogenic mechanisms involved in CMT mutations related to neddylation.
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