title: Ndel1 promotes axon regeneration via intermediate filaments.
abstract: Failure of axons to regenerate following acute or chronic neuronal injury is attributed to both the inhibitory glial environment and deficient intrinsic ability to re-grow. However, the underlying mechanisms of the latter remain unclear. In this study, we have investigated the role of the mammalian homologue of aspergillus nidulans NudE, Ndel1, emergently viewed as an integrator of the cytoskeleton, in axon regeneration. Ndel1 was synthesized de novo and upregulated in crushed and transected sciatic nerve axons, and, upon injury, was strongly associated with neuronal form of the intermediate filament (IF) Vimentin while dissociating from the mature neuronal IF (Neurofilament) light chain NF-L. Consistent with a role for Ndel1 in the conditioning lesion-induced neurite outgrowth of Dorsal Root Ganglion (DRG) neurons, the long lasting in vivo formation of the neuronal Ndel1/Vimentin complex was associated with robust axon regeneration. Furthermore, local silencing of Ndel1 in transected axons by siRNA severely reduced the extent of regeneration in vivo. Thus, Ndel1 promotes axonal regeneration; activating this endogenous repair mechanism may enhance neuroregeneration during acute and chronic axonal degeneration.
authors.affiliation: Department of Clinical Neurosciences, University of Calgary, Hotchkiss Brain Institute, Calgary, Canada.
authors.forename: Cory
authors.initials: C
authors.lastname: Toth
authors.forename: Su Yeon
authors.initials: SY
authors.lastname: Shim
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Yulan
authors.initials: Y
authors.lastname: Jiang
authors.forename: Gernot
authors.initials: G
authors.lastname: Neumayer
authors.forename: Camille
authors.initials: C
authors.lastname: Belzil
authors.forename: Wei-Qiao
authors.initials: WQ
authors.lastname: Liu
authors.forename: Jose
authors.initials: J
authors.lastname: Martinez
authors.forename: Douglas
authors.initials: D
authors.lastname: Zochodne
authors.forename: Minh Dang
authors.initials: MD
authors.lastname: Nguyen
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000473:pathology; D007382:Intermediate Filaments / Q000378:metabolism*; D051379:Mice; D009409:Nerve Crush; D009416:Nerve Regeneration; D016501:Neurites / Q000473:pathology; D016900:Neurofilament Proteins / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D034622:RNA Interference; D034741:RNA, Small Interfering; D051381:Rats; D012584:Sciatic Nerve / Q000473:pathology; D015854:Up-Regulation; D014746:Vimentin / Q000235:genetics
chemical_list: D002352:Carrier Proteins; C486015:Ndel1 protein, mouse; D016900:Neurofilament Proteins; D034741:RNA, Small Interfering; D014746:Vimentin; C044882:neurofilament protein L