Neddylation orchestrates the complex transcriptional and posttranscriptional program that drives Schwann cell myelination-Reference-Cited by-同舟云学术

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

Published:2024-04-12 Issue:15 Volume:10 Page:
ISSN:2375-2548
Container-title:Science Advances
language:en
Short-container-title:Sci. Adv.

Author:

Ayuso-García Paula¹^ORCID,Sánchez-Rueda Alejandro¹^ORCID,Velasco-Avilés Sergio¹^ORCID,Tamayo-Caro Miguel²^ORCID,Ferrer-Pinós Aroa¹^ORCID,Huarte-Sebastian Cecilia¹^ORCID,Alvarez Vanesa¹^ORCID,Riobello Cristina¹^ORCID,Jiménez-Vega Selene¹^ORCID,Buendia Izaskun¹³^ORCID,Cañas-Martin Jorge¹^ORCID,Fernández-Susavila Héctor¹^ORCID,Aparicio-Rey Adrián¹^ORCID,Esquinas-Román Eva M.¹^ORCID,Ponte Carlos Rodríguez¹,Guhl Romane¹⁴^ORCID,Laville Nicolas¹⁴^ORCID,Pérez-Andrés Encarni²^ORCID,Lavín José L.²⁵^ORCID,González-Lopez Monika²^ORCID,Cámara Nuria Macías²^ORCID,Aransay Ana M.²⁶^ORCID,Lozano Juan José⁶^ORCID,Sutherland James D.²^ORCID,Barrio Rosa²^ORCID,Martinez-Chantar María Luz²⁶^ORCID,Azkargorta Mikel²,Elortza Félix²^ORCID,Soriano-Navarro Mario⁷^ORCID,Matute Carlos³⁸⁹^ORCID,Sánchez-Gómez María Victoria³⁸⁹^ORCID,Bayón-Cordero Laura³⁸⁹^ORCID,Pérez-Samartín Alberto³⁸⁹^ORCID,Bravo Susana B.¹⁰^ORCID,Kurz Thimo¹¹^ORCID,Lama-Díaz Tomas¹²^ORCID,Blanco Miguel G.¹²¹³^ORCID,Haddad Saif¹⁴^ORCID,Record Christopher J.¹⁴^ORCID,van Hasselt Peter M.¹⁵^ORCID,Reilly Mary M.¹⁴^ORCID,Varela-Rey Marta¹¹³^ORCID,Woodhoo Ashwin¹²¹⁶¹⁷¹⁸^ORCID

Affiliation:

1. Gene Regulatory Control in Disease Laboratory, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), University of Santiago de Compostela, 15706 Santiago de Compostela, A Coruña, Spain.

2. Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, 48160 Derio, Spain.

3. Laboratory of Neurobiology, Achucarro Basque Center for Neuroscience, Science Park of UPV/EHU, Sede building, 48940 Leioa, Spain.

4. Université Paris Cité Magistère Européen de Génétique, 85 Boulevard Saint-Germain, 75006 Paris, France.

5. NEIKER–Basque Institute for Agricultural Research and Development, Applied Mathematics Department, Bioinformatics Unit, Basque Research and Technology Alliance (BRTA), 48160 Derio, Bizkaia, Spain.

6. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.

7. Electron Microscopy Core Facility, Centro de Investigación Príncipe Felipe (CIPF), 46012 Valencia, Spain.

8. Department of Neurosciences, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain.

9. Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), 28031 Madrid, Spain.

10. Proteomic Unit, Health Research Institute of Santiago de Compostela (IDIS), 15705 Santiago de Compostela, A Coruña, Spain.

11. Evotec SE, Innovation Dr, Milton, Abingdon OX14 4RT, UK and School of Molecular Biosciences, University of Glasgow, Glasgow G12 8QQ, UK.

12. DNA Repair and Genome Integrity Laboratory, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, 15706 Santiago de Compostela, A Coruña, Spain.

13. Department of Biochemistry and Molecular Biology, University of Santiago de Compostela, Plaza do Obradoiro s/n, Santiago de Compostela, Spain.

14. Centre for Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK.

15. Department of Metabolic Diseases, Division Pediatrics, Wilhelmina Children’s Hospital University Medical Center Utrecht, Utrecht University, 3584 EA, Utrecht, Netherlands.

16. IKERBASQUE, Basque Foundation for Science, 48009 Bilbao, Bizkaia, Spain.

17. Department of Functional Biology, University of Santiago de Compostela, Plaza do Obradoiro s/n, Santiago de Compostela, Spain.

18. Oportunius Research Professor at CIMUS/USC, Galician Agency of Innovation (GAIN), Xunta de Galicia, Santiago de Compostela, A Coruña, Spain.

Abstract

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.

Publisher

American Association for the Advancement of Science (AAAS)

Link

https://www.science.org/doi/pdf/10.1126/sciadv.adm7600

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