Schwann cells, but not Oligodendrocytes, Depend Strictly on Dynamin 2 Function

eLife

Valentina Tadini¹  Monica Ghidinelli¹  Jorge A Pereira¹  Lukas G Nägeli¹  Vanessa Suter¹  Daniel Gerber¹  Páris NM Sidiropoulos¹  Christian Somandin¹  Andrea Ommer¹  Michaela Miehe¹  Ueli Suter¹  Elisa Tinelli¹  Gianluca Figlia¹  Joanne Gerber¹  Klaus V Toyka²  Carsten Wessig² 

[1] Department of Biology, Institute of Molecular Health Sciences, Swiss Federal Institute of Technology, ETH Zurich, Zurich, Switzerland;Department of Neurology, University Hospital of Würzburg, University of Würzburg, Würzburg, Germany;

关键词: Myelination;    Demyelination;    Charcot-Marie-Tooth Disease;    Neuropathy;    Schwann cells;    Oligodendrocytes;   

DOI  :  10.7554/eLife.42404

来源: DOAJ

【 摘 要 】

Myelination requires extensive plasma membrane rearrangements, implying that molecules controlling membrane dynamics play prominent roles. The large GTPase dynamin 2 (DNM2) is a well-known regulator of membrane remodeling, membrane fission, and vesicular trafficking. Here, we genetically ablated Dnm2 in Schwann cells (SCs) and in oligodendrocytes of mice. Dnm2 deletion in developing SCs resulted in severely impaired axonal sorting and myelination onset. Induced Dnm2 deletion in adult SCs caused a rapidly-developing peripheral neuropathy with abundant demyelination. In both experimental settings, mutant SCs underwent prominent cell death, at least partially due to cytokinesis failure. Strikingly, when Dnm2 was deleted in adult SCs, non-recombined SCs still expressing DNM2 were able to remyelinate fast and efficiently, accompanied by neuropathy remission. These findings reveal a remarkable self-healing capability of peripheral nerves that are affected by SC loss. In the central nervous system, however, we found no major defects upon Dnm2 deletion in oligodendrocytes.

【 授权许可】

Unknown