title: Vimentin regulates peripheral nerve myelination.
abstract: 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.
authors.affiliation: Institute of Experimental Neurology, San Raffaele Scientific Institute, Via Olgettina 60, Milan, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Triolo
authors.forename: Giorgia
authors.initials: G
authors.lastname: Dina
authors.forename: Carla
authors.initials: C
authors.lastname: Taveggia
authors.forename: Ilaria
authors.initials: I
authors.lastname: Vaccari
authors.forename: Emanuela
authors.initials: E
authors.lastname: Porrello
authors.forename: Cristina
authors.initials: C
authors.lastname: Rivellini
authors.forename: Teuta
authors.initials: T
authors.lastname: Domi
authors.forename: Rosa
authors.initials: R
authors.lastname: La Marca
authors.forename: Federica
authors.initials: F
authors.lastname: Cerri
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bolino
authors.forename: Angelo
authors.initials: A
authors.lastname: Quattrini
authors.forename: Stefano Carlo
authors.initials: SC
authors.lastname: Previtali
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000072198:ADAM17 Protein; D000818:Animals; D001369:Axons / Q000378:metabolism; D018920:Coculture Techniques; D003599:Cytoskeleton / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006579:Heterozygote; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009186:Myelin Sheath / Q000378:metabolism*; D020890:Neuregulin-1 / Q000378:metabolism; D010525:Peripheral Nerves / Q000378:metabolism*; D051381:Rats; D012583:Schwann Cells / Q000166:cytology; D014746:Vimentin / Q000502:physiology*
chemical_list: D020890:Neuregulin-1; C490581:Nrg1 protein, mouse; C490580:Nrg1 protein, rat; D014746:Vimentin; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human; C000606463:Adam17 protein, mouse; C000606464:Adam17 protein, rat