Figure 7.

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 signaling endosome, including downstream messengers, is retrogradely transported by microtubule-dependent dynein motors. C, On reaching the cell body, phosphorylated ERK5 translocates to the nucleus. D, MEF2D is phosphorylated and activated in response to a retrograde ERK5 signal. E, Activated MEF2D initiates transcription of bcl-w, mef2d, and other retrograde response genes (RRGs) to promote survival mediated by target-derived neurotrophins. F, In the case of cell body neurotrophin stimulation, both ERK5 and ERK1/2 are activated; however, expression of bcl-w, mef2d, and other retrograde response genes are not induced. One possible mechanism is through suppression of ERK5 by the ERK1/2 pathway.