Axonal transport of activating transcription factor-2 is modulated by nerve growth factor in nociceptive neurons.
The aim of this study was to determine whether axonal transport of activating transcription factor-2 (ATF2) occurs in adult sensory neurons, and whether this process is under neurotrophin control. Antisera to both total ATF2 and to the activated (i.e., phosphorylated) form were used for immunocytochemistry and Western blotting. ATF2 was localized to predominantly nociceptive dorsal root ganglion cells in adult rats and shown to accumulate proximal and distal to a sciatic nerve ligature as a result of axonal transport. Subcutaneous injection of nerve growth factor (NGF) decreased the levels of fast retrograde axonal transport of activated ATF2 by 97% (p < 0.05) and elevated levels of retrograde axonal transport of total ATF2 by twofold (p < 0.02). In contrast, blocking endogenous NGF using an anti-NGF antibody induced an elevation in retrograde axonal transport of activated ATF2 of 4. 5-fold (p < 0.05) and decreased retrograde axonal transport of total ATF2 by 72% (p < 0.05). NGF or anti-NGF treatment had no effect on the anterograde transport levels of total or activated ATF2. This study shows that signaling by target-derived NGF to the cell bodies of sensory neurons consists, in part, of the modulation of levels and activation status of a retrogradely transported transcription factor, ATF2.
Delcroix
J D
JD
Division of Neuroscience, School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom.
Averill
S
S
Fernandes
K
K
Tomlinson
D R
DR
Priestley
J V
JV
Fernyhough
P
P
D051698:Activating Transcription Factor 2; D000818:Animals; D001370:Axonal Transport; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D019084:Fluorescent Antibody Technique, Indirect; D005727:Ganglia, Spinal / Q000378:metabolism; D008161:Lumbosacral Region; D008297:Male; D020932:Nerve Growth Factor / Q000494:pharmacology / Q000502:physiology*; D009475:Neurons, Afferent / Q000378:metabolism / Q000502:physiology*; D009619:Nociceptors / Q000166:cytology / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
D051698:Activating Transcription Factor 2; C497107:Atf2 protein, rat; D017362:Cyclic AMP Response Element-Binding Protein; D014157:Transcription Factors; D020932:Nerve Growth Factor