Target-derived NGF mediates axon growth and synapse assembly in sympathetic neurons via endocytic signaling mechanisms. (a) Retrograde NGF signaling, likely via axonal transport of TrkA-signaling endosomes, activates transcription factors and the expression of downstream target genes essential for long-term axon growth and target innervation. (b) Local NGF-TrkA signaling from an endocytic platform in axons promotes axon growth. NGF-TrkA complexes are endocytosed via a signaling pathway that includes Phospholipase C-γ, calcineurin and dynamin1. Internalization of TrkA in distal axons is required for short-term axon growth, in a manner independent of transcriptional responses. (c) NGF-TrkA signaling endosomes are retrogradely transported long-distance from axon terminals to the distal dendrites of sympathetic neurons. In dendrites, NGF-TrkA endosomal complexes signal via the MEK/MAPK pathway to regulate the clustering of acetylcholine receptors (nAChRs) and pre-existing postsynaptic density components including MAGUK, GKAP and Shank. Endosomal TrkA signaling modulates the assembly of postsynaptic components, in part, by restricting the anti-synaptic actions of p75 signaling in dendrites.