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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


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