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

• DOI: 10.1126/sciadv.adm7600
• Publication Date: 2024-04-12T17:58:21Z
• Authors: Paula Ayuso-García; Alejandro Sánchez...; Sergio Velasco-Av...; Miguel Tamayo-Caro; Aroa Ferrer-Pinós; Cecilia Huarte-Se...; Vanesa Alvarez; Cristina Riobello; Selene Jiménez-Vega; Izaskun Buendia; Jorge Cañas-Martin; Héctor Fernández-...; Adrián Aparicio-Rey; Eva M. Esquinas-R...; Carlos Rodríguez ...; Romane Guhl; Nicolas Laville; Encarni Pérez-Andrés; José L. Lavín; Monika González-L...; Nuria Macías Cámara; Ana M. Aransay; Juan José Lozano; James D. Sutherland; Rosa Barrio; María Luz Martine...; Mikel Azkargorta; Félix Elortza; Mario Soriano-Nav...; Carlos Matute; María Victoria Sá...; Laura Bayón-Cordero; Alberto Pérez-Sam...; Susana B. Bravo; Thimo Kurz; Tomas Lama-Díaz; Miguel G. Blanco; Saif Haddad; Christopher J. Re...; Peter M. van Hasselt; Mary M. Reilly; Marta Varela-Rey; Ashwin Woodhoo
• Keywords: Neddylation; Crosstalk; Schwann cell; Citrullination

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 can affect myelin sheaths. Among these, number of are related to targets the posttranslational modification neddylation, although how these lead defects unclear. Here, we demonstrate inhibiting neddylation leads notable absence axonal loss both in developing regenerating mouse nerves. Our data indicate exerts global influence on complex transcriptional posttranscriptional program by simultaneously regulating expression multiple myelination signals, including master transcription factor EGR2 negative regulators c-Jun Sox2, inducing secondary changes downstream pathways, mTOR YAP/TAZ signaling pathways. This places as critical regulator delineates potential pathogenic mechanisms involved CMT neddylation.