TY - JOUR
T1 - Satellite glia not DRG neurons constitutively activate EGFR but EGFR inactivation is not correlated with axon regeneration
AU - Ahmed, Zubair
AU - Read, Martin
AU - Berry, Martin
AU - Logan, Ann
PY - 2010/9/1
Y1 - 2010/9/1
N2 - 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 knock-down 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.
AB - 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 knock-down 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.
KW - EGFR
KW - siRNA
KW - DRGN
KW - Axon/neurite growth
KW - DRG satellite glia
UR - https://www.scopus.com/pages/publications/77954952488
U2 - 10.1016/j.nbd.2010.04.013
DO - 10.1016/j.nbd.2010.04.013
M3 - Article
C2 - 20451608
VL - 39
SP - 292
EP - 300
JO - Neurobiology of Disease
JF - Neurobiology of Disease
IS - 3
ER -