On Trk for retrograde signaling.

ABSTRACT

Target-derived neurotrophins like nerve growth factor (NGF) mediate biological effects by binding to and activating Trk neurotrophin receptors at nerve terminals. The activated Trk receptors then stimulate local effects at nerve terminals, and retrograde effects at neuronal cell bodies that often reside at considerable distances from the terminals. However, the nature of the retrograde signal has been mysterious. Recent experiments suggest that the major retrograde signal required for survival and gene expression consists of activated Trk itself. Remarkably, signaling by Trk may differ at the terminal versus the neuronal cell body as a consequence of the retrograde transport mechanism, thereby allowing NGF to not only promote growth locally, but to specifically support survival and gene expression retrogradely.