title: Vimentin phosphorylation by Cdc2 in Schwann cell controls axon growth via β1-integrin activation.
abstract: Although preconditioning injury on the peripheral nerve induces axonal regenerative capacity in neurons, it is not known whether similar lesion effects occur in glial cells. Here we demonstrate that Schwann cells are activated by peripheral nerve preinjury and primed to mediate axon regeneration. Cdc2, which was induced from Schwann cells after sciatic nerve injury, phosphorylated vimentin almost exclusively in the distal nerve area. Phospho-vimentin-positive Schwann cells showed increased migration activity and were in close contact with process outgrowth of co-cultured neurons. Vimentin phosphorylation by Cdc2 was involved in β1-integrin activation leading to FAK phoshorylation and associated with Erk1/2 activation in Schwann cells. Neurite outgrowth of dorsal root ganglion neurons was increased by co-culture with activated Schwann cells, in which phospho-vimentin signaling was transmitted into β1-integrin activation. Then neurite outgrowth was suppressed by genetic depletion of phospho-vimentin and β1 integrin as well as inhibition of vimentin phosphorylation by Cdc2 inhibitor purvalanol A. The sciatic nerve graft harboring activated Schwann cells into the spinal cord induced Schwann cell migration beyond the graft-host barrier and facilitated regeneration of spinal axons, which was inhibited by purvalanol A pretreatment of the graft. This is the first report to our knowledge demonstrating that activation of phospho-vimentin linked to β1-integrin pathway may mediate transcellular signaling to promote axon growth.
authors.affiliation: Department of Oriental Medicine, Daejeon University, Daejeon 300-716, Republic of Korea.
authors.forename: In Ae
authors.initials: IA
authors.lastname: Chang
authors.forename: Myung-Jin
authors.initials: MJ
authors.lastname: Oh
authors.forename: Min Hee
authors.initials: MH
authors.lastname: Kim
authors.forename: Seung-Kiel
authors.initials: SK
authors.lastname: Park
authors.forename: Byung G
authors.initials: BG
authors.lastname: Kim
authors.forename: Uk
authors.initials: U
authors.lastname: Namgung
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D018920:Coculture Techniques; D018844:Cyclin-Dependent Kinases; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005727:Ganglia, Spinal / Q000187:drug effects / Q000502:physiology; D019012:Integrin beta1 / Q000378:metabolism*; D009416:Nerve Regeneration / Q000502:physiology*; D016501:Neurites / Q000502:physiology; D010766:Phosphorylation; D011687:Purines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000187:drug effects / Q000378:metabolism* / Q000637:transplantation; D012584:Sciatic Nerve / Q000293:injuries; D014746:Vimentin / Q000378:metabolism*
chemical_list: C471843:6-((3-chloro)anilino)-2-(isopropyl-2-hydroxyethylamino)-9-isopropylpurine; D018797:Cell Cycle Proteins; D019012:Integrin beta1; D011687:Purines; D014746:Vimentin; D016203:CDC2 Protein Kinase; C548796:Cdk1 protein, rat; D018844:Cyclin-Dependent Kinases; D048049:Extracellular Signal-Regulated MAP Kinases