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Vimentin phosphorylation by Cdc2 in Schwann cell controls axon growth via β1-integrin activation

Authors
Chang, IA; Oh, MJ; Kim, MH; Park, SK; Kim, BG; Namgung, U
Citation
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 26(6):2401-2413, 2012
Journal Title
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN
0892-66381530-6860
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.
MeSH terms
AnimalsAntigens, CD29/*metabolismAxons/*physiologyCDC2 Protein Kinase/*metabolismCell Cycle Proteins/*metabolismCell Movement/drug effectsCoculture TechniquesExtracellular Signal-Regulated MAP Kinases/metabolismGanglia, Spinal/drug effects/physiologyNerve Regeneration/*physiologyNeurites/physiologyPhosphorylationPurines/pharmacologyRatsRats, Sprague-DawleySchwann Cells/drug effects/*metabolism/transplantationSciatic Nerve/injuriesVimentin/*metabolism
DOI
10.1096/fj.11-199018
PMID
22371530
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Brain Science
AJOU Authors
김, 병곤
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