During the formation of neuronal circuits, neurons respond to diffusible cues secreted by target tissues. Often, target-derived signals act on nerve terminals to influence local growth events; in other cases, they are transported long distances back to neuronal cell bodies to effect transcriptional changes necessary for neuronal survival and differentiation. Neurotrophins provide one of the best examples of target-derived cues that elicit an astonishingly diverse array of neuronal responses. Endocytic trafficking of neurotrophins and their receptors is a fundamental feature of neurotrophin signaling, allowing neurotrophins to control neuronal survival by retrograde transport of signaling endosomes containing ligand-receptor complexes. In this review we summarize recent findings that provide new insight into the interplay between neurotrophin signaling and trafficking.
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