Ndel1 Promotes Axon Regeneration via Intermediate Filaments

• DOI: 10.1371/journal.pone.0002014
• Publication Date: 2008-04-22T23:28:28Z
• Authors: Cory Toth; Su Yeon Shim; Jian Wang; Yulan Jiang; Gernot Neumayer; Camille Belzil; Wei-Qiao Liu; Jose Martinez; Douglas Zochodne; Minh Dang Nguyen
• Keywords: 0301 basic medicine; 571; Nerve Crush; Science; Intermediate Filaments; Neuroscience/Neural Homeostasis; Neurological Disorders/Multiple Sclerosis and Related Disorders; Cell Biology/Cell Signaling; Mice; 03 medical and health sciences; Neurofilament Proteins; Cell Biology/Cytoskeleton; Ganglia, Spinal; Neuroscience/Neuronal Signaling Mechanisms; Neurites; Animals; Vimentin; RNA, Small Interfering; Neurological Disorders/Movement Disorders; Neuroscience/Neuronal and Glial Cell Biology; Q; R; Cell Biology; Cell Biology/Cellular Death and Stress Responses; Neuroscience/Neurodevelopment; Sciatic Nerve; Axons; Nerve Regeneration; Rats; Up-Regulation; Protein Transport; Cell Biology/Neuronal and Glial Cell Biology; Medicine; Cell Biology/Morphogenesis and Cell Biology; RNA Interference; Neuroscience/Neurobiology of Disease and Regeneration; Carrier Proteins; Neurological Disorders/Alzheimer Disease; Neuroscience; Research Article; Protein Binding

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.