Neurotrophin signaling endosomes: biogenesis, regulation, and functions

• Neurotrophin-bound Trk receptors form signaling endosomes in growth cones.
• Trk signaling controls it's own internalization and axonal transport.
• Retrogradely transported endosomes activate trophic signaling pathways in soma.
• Neurotrophin endosomes are transported to dendrites to regulate synaptic connectivity.
• Impaired neurotrophin trafficking may contribute to neurodevelopmental disorders.

In the nervous system, communication between neurons and their post-synaptic target cells is critical for the formation, refinement and maintenance of functional neuronal connections. Diffusible signals secreted by target tissues, exemplified by the family of neurotrophins, impinge on nerve terminals to influence diverse developmental events including neuronal survival and axonal growth. Key mechanisms of action of target-derived neurotrophins include the cell biological processes of endocytosis and retrograde trafficking of their Trk receptors from growth cones to cell bodies. In this review, we summarize the molecular mechanisms underlying this endosome-mediated signaling, focusing on the instructive role of neurotrophin signaling itself in directing its own trafficking. Recent studies have linked impaired neurotrophin trafficking to neurodevelopmental disorders, highlighting the relevance of neurotrophin endosomes in human health.