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 activati ng transcription factor-2 (ATF2) occurs in adult sensory neurons, and wheth er this process is under neurotrophin control. Antisera to both total ATF2 and to the activated (i.e., phosphorylated) form were used for immunocytoch emistry and Western blotting. ATF2 was localized to predominantly nocicepti ve dorsal root ganglion cells in adult rats and shown to accumulate proxima l and distal to a sciatic nerve ligature as a result of axonal transport. S ubcutaneous injection of nerve growth factor (NGF) decreased the levels of fast retrograde axonal transport of activated ATF2 by 97% (p < 0.05) and el evated levels of retrograde axonal transport of total ATF2 by twofold (p < 0.02). In contrast, blocking endogenous NGF using an anti-NGF antibody indu ced an elevation in retrograde axonal transport of activated ATF2 of 4.5-fo ld (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 tr ansport levels of total or activated ATF2. This study shows that signaling by target-derived NGF to the cell bodies of sensory neurons consists, in pa rt, of the modulation of levels and activation status of a retrogradely tra nsported transcription factor, ATF2.