Ndel1 promotes axon regeneration via intermediate filaments.
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.
Toth
Cory
C
Department of Clinical Neurosciences, University of Calgary, Hotchkiss Brain Institute, Calgary, Canada.
Shim
Su Yeon
SY
Wang
Jian
J
Jiang
Yulan
Y
Neumayer
Gernot
G
Belzil
Camille
C
Liu
Wei-Qiao
WQ
Martinez
Jose
J
Zochodne
Douglas
D
Nguyen
Minh Dang
MD
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
D002352:Carrier Proteins; C486015:Ndel1 protein, mouse; D016900:Neurofilament Proteins; D034741:RNA, Small Interfering; D014746:Vimentin; C044882:neurofilament protein L