Differences in the retrograde axonal transport of nerve growth factor and dopamine beta‐hydroxylase

Abstract

There are two potential populations of vesicles in the sympathetic nervous system that may contribute to the retrograde axonal transport of signals from the target tissue. These are derived from the population of recycled synaptic vesicles and endosomes derived from receptor mediated endocytosis of growth factors. We have analysed the retrograde axonal transport of two l125‐labelled marker proteins, nerve growth factor (NGF) and dopamine beta‐hydroxylase (d.b.h.), to determine whether these two populations are processed in the same way in the nerve terminal. Two models were used in the rat, either from the anterior eye chamber to the superior cervical ganglion and trigeminal ganglion or the ligated sciatic nerve after injection into the footpad. The results show that there are significant differences in the regulatory processes that control the targeting of these proteins for retrograde transport. Many inhibitors of the second messenger cascades inhibit the transport of both molecules, for example Latrunculin A and wortmannin. However, the retrograde axonal transport of NGF is inhibited by phenylarsine oxide but not by bis‐tyrphostin, FK506, dibutyryl‐cAMP, thapsigargin, cadmium and nickel whereas the transport of d.b.h. is the reverse, suggesting the mechanism of endocytosis and targeting the vesicles in the nerve terminal for retrograde axonal transport is different. We have isolated vesicles labelled with these iodinated proteins from the sciatic nerve and have shown that the density of the NGF containing vesicles is significantly lighter than those containing d.b.h. This suggests that there are at least two distinct pathways for retrograde axonal transport of vesicles.