Neurotrophin signalling in the nervous system

Neurotrophins appear to have important trophic roles in thedeveloping and mature nervous system. The discovery that members of the trk gene family are signalling receptors for the neurotrophins suggests that studies of trk gene expression will be informative with respect to the locus, timing and biological significance of neurotrophin actions. NGF is a target-derived neurotrophin. Localization of trkA expression is predictive of NGF responsiveness in neurons in both the PNS and CNS. The onset of trk expression in the developing PNS appears to allow for NGF signalling as soon as neurites contact NGF in the target. Studies on NGF and trkA raise the possibility that neurotrophins may normally act via internalization of their trk receptors with subsequent retrograde transport of the activated receptor from the neurite tip to the cell body. In the CNS and in PC12 cells, trkA gene expression is induced by NGF. Regulation of trkA by NGF may compensate for receptor internalization and degradation. The localization of expression for trkB and C is more widespread than trkA, and novel trophic relationships are suggested by the complicated, sometimes overlapping patterns for BDNF and NT-3 and their corresponding trk mRNAs. While for some neurons the actions of BDNF, NT-3 and NT-4/5 may be similar to NGF, in other cases there may be autocrine or paracrine modes of action. Understanding where and how activated trk's signal is key to elucidating the actions of NGF and the other neurotrophins.