The Journal of Neuroscience, 1999, 0:RC24:1-7
RAPID COMMUNICATION
Axonal Transport of Activating Transcription Factor-2 Is
Modulated by Nerve Growth Factor in Nociceptive Neurons
Jean-Dominique
Delcroix1,
Sharon
Averill2,
Karin
Fernandes1,
David R.
Tomlinson1,
John V.
Priestley2, and
Paul
Fernyhough1
1 Division of Neuroscience, School of Biological
Sciences, University of Manchester, Manchester M13 9PT, United Kingdom,
and 2 Neuroscience Section, Division of Biomedical
Sciences, St. Bartholomew's and The Royal London School of Medicine
and Dentistry, Queen Mary and Westfield College, University of London,
London E1 4NS, United Kingdom
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.
Key words:
adult rat; dorsal root ganglion; nerve growth factors; neurotrophin; phosphorylation; sciatic nerve; sensory neuron; signal
transduction
Copyright © 0000 Society for Neuroscience 0270-6474/0/$05.00/0