Abstract
Fibroblast growth factors (FGFs) play a prominent role in axonal growth during development and repair. Treatment with FGF-2 or overexpression of FGF receptors promotes peripheral axon regeneration mainly by activation of extracellular signal-regulated kinase (ERK). The Ras/Raf/ERK pathway is under the control of Sprouty proteins acting as negative feedback inhibitors. We investigated the expression of Sprouty isoforms in adult sensory neurons of dorsal root ganglia (DRG) as well as the effects of Sprouty inhibition on axon growth by small interfering RNAs (siRNAs). Sprouty2 revealed the highest expression level in DRG neurons. Down-regulation of Sprouty2 promoted elongative axon growth by adult sensory neurons accompanied by enhanced FGF-2-induced activation of ERK and Ras, whereas Sprouty2 overexpression inhibited axon growth. Sprouty2 was not regulated in vivo in response to a sciatic nerve lesion. Together, our results imply that Sprouty2 is highly expressed in adult peripheral neurons and its down-regulation strongly promotes elongative axon growth by activation of the Ras/Raf/ERK pathway.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Animals
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Axons / physiology*
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Axons / ultrastructure
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Down-Regulation*
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Enzyme Activation
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Extracellular Signal-Regulated MAP Kinases / genetics
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Female
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Fibroblast Growth Factor 2 / metabolism
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Ganglia, Spinal / cytology*
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Ganglia, Spinal / metabolism
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Mice
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NIH 3T3 Cells
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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PC12 Cells
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Protein Isoforms / genetics
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Protein Isoforms / metabolism*
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Protein Serine-Threonine Kinases
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RNA, Small Interfering / genetics
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RNA, Small Interfering / metabolism
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Rats
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Rats, Sprague-Dawley
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Receptors, Fibroblast Growth Factor / genetics
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Receptors, Fibroblast Growth Factor / metabolism
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Sensory Receptor Cells* / physiology
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Sensory Receptor Cells* / ultrastructure
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Signal Transduction / physiology
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raf Kinases / genetics
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raf Kinases / metabolism
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ras Proteins / genetics
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ras Proteins / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Nerve Tissue Proteins
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Protein Isoforms
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RNA, Small Interfering
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Receptors, Fibroblast Growth Factor
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Spry2 protein, rat
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Fibroblast Growth Factor 2
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Protein Serine-Threonine Kinases
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Spry2 protein, mouse
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raf Kinases
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Extracellular Signal-Regulated MAP Kinases
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ras Proteins