Vimentin regulates peripheral nerve myelination
| Autor: | Stefano C. Previtali, Teuta Domi, Daniela Triolo, Emanuela Porrello, Cristina Rivellini, Federica Cerri, Rosa La Marca, Angelo Quattrini, Giorgia Dina, Alessandra Bolino, Ilaria Vaccari, Carla Taveggia |
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| Rok vydání: | 2012 |
| Předmět: |
Heterozygote
Neuregulin-1 Schwann cell Vimentin macromolecular substances ADAM17 Protein Biology Mice Myelin mental disorders medicine Animals Humans Peripheral Nerves Neuregulin 1 Intermediate filament Cytoskeleton Molecular Biology Myelin Sheath Regeneration (biology) Gene Expression Regulation Developmental Cell Biology Axons Coculture Techniques Rats Cell biology Mice Inbred C57BL ADAM Proteins medicine.anatomical_structure nervous system Immunology biology.protein Schwann Cells Neuron Developmental Biology |
| Zdroj: | Development. 139:1359-1367 |
| ISSN: | 1477-9129 0950-1991 |
| Popis: | Myelination is a complex process that requires coordinated Schwann cell-axon interactions during development and regeneration. Positive and negative regulators of myelination have been recently described, and can belong either to Schwann cells or neurons. Vimentin is a fibrous component present in both Schwann cell and neuron cytoskeleton, the expression of which is timely and spatially regulated during development and regeneration. We now report that vimentin negatively regulates myelination, as loss of vimentin results in peripheral nerve hypermyelination, owing to increased myelin thickness in vivo, in transgenic mice and in vitro in a myelinating co-culture system. We also show that this is due to a neuron-autonomous increase in the levels of axonal neuregulin 1 (NRG1) type III. Accordingly, genetic reduction of NRG1 type III in vimentin-null mice rescues hypermyelination. Finally, we demonstrate that vimentin acts synergistically with TACE, a negative regulator of NRG1 type III activity, as shown by hypermyelination of double Vim/Tace heterozygous mice. Our results reveal a novel role for the intermediate filament vimentin in myelination, and indicate vimentin as a regulator of NRG1 type III function. |
| Databáze: | OpenAIRE |
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