THERE AND BACK AGAIN: NEUROTROPHIN REGULATION OF AXONAL VIABILITY

In order for target-derived neurotrophins to regulate the survival of a developing presynaptic cell, a signal must be propagated from the nerve terminal along the axon to the nucleus. We found that activated Trk receptors function as rapid retrograde signal carriers to elicit neuclear responses to target derived neurotrophins. Our data indicate that the mechanism of signal propagation is retrograde vesicular transport of activated Trk-ligand complexes. Once they reach the cell body, activated receptors elicit nuclear responses-including phosphorylation of the transcription factor CREB and subsequent induction of the immediate early gene c-fos. We are currently studying other intermediates required for retrograde signaling and the potential differences in the biological responses to retrograde or local stimulation with growth factors. Target-derived neurotrophins activate an ERK5/MEF2 transcriptional program to promote survival. A, Neurotrophin binding and Trk activation results in endocytosis of the activated receptor complex. B, The signalin