Satellite glia not DRG neurons constitutively activate EGFR but EGFR inactivation is not correlated with axon regeneration.
To test the possibility that phosphorylated epidermal growth factor receptor (pEGFR) mediates axon growth inhibition, we determined if pEGFR levels were raised in dorsal root ganglia (DRG) after non-regenerating dorsal column (DC) lesions and suppressed in regenerating sciatic nerve (SN) and preconditioning (P) SN+DC lesioned DRG. Levels of EGFR mRNA and protein in DRG were unchanged between control and all injury models. Satellite glia and not DRG neurons (DRGN) constitutively contained pEGFR and, only in PSN+DC rats, were levels significantly reduced in these cells. In vitro, siRNA mediated knockdown of EGFR (siEGFR) mRNA and protein was associated with suppressed RhoA activation, but fibroblast growth factor-2 (FGF2) was a mandatory requirement for DRGN neuritogenesis after addition of inhibitory concentrations of CNS myelin. Thus, EGFR activation in satellite glia was not consistently correlated with DRGN axogenesis and siEGFR reduction of pEGFR with attenuated Rho-GTP signalling did not promote DRGN disinhibited neurite outgrowth without exogenous FGF2 stimulation. Together, these data argue against a direct intra-axonal involvement of pEGFR in axon regeneration.
Ahmed
Zubair
Z
Molecular Neuroscience Group, Neuropharmacology and Neurobiology Section, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK. z.ahmed.1@bham.ac.uk
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Martin L
ML
Berry
Martin
M
Logan
Ann
A
D051700:Activating Transcription Factor 3 / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001369:Axons / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D066246:ErbB Receptors / Q000378:metabolism*; D019922:GAP-43 Protein / Q000378:metabolism; D019004:Galanin / Q000378:metabolism; D005727:Ganglia, Spinal / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000502:physiology*; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009478:Neuropeptide Y / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012584:Sciatic Nerve / Q000502:physiology*
D051700:Activating Transcription Factor 3; D019922:GAP-43 Protein; D009478:Neuropeptide Y; D019004:Galanin; D066246:ErbB Receptors