Mechanisms of neurotrophin trafficking via Trk receptors

In neurons, long-distance communication between axon terminals and cell bodies is a critical determinant in establishing and maintaining neural circuits. Neurotrophins are soluble factors secreted by post-synaptic target tissues that retrogradely control axon and dendrite growth, survival, and synaptogenesis of innervating neurons. Neurotrophins bind Trk receptor tyrosine kinases in axon terminals to promote endocytosis of ligand-bound phosphorylated receptors into signaling endosomes. Trk-harboring endosomes function locally in axons to acutely promote growth events, and can also be retrogradely transported long-distances to remote cell bodies and dendrites to stimulate cytoplasmic and transcriptional signaling necessary for neuron survival, morphogenesis, and maturation. Neuronal responsiveness to target-derived neurotrophins also requires the precise axonal targeting of newly synthesized Trk receptors. Recent studies suggest that anterograde delivery of Trk receptors is regulated by retrograde neurotrophin signaling. In this review, we summarize current knowledge on the functions and mechanisms of retrograde trafficking of Trk signaling endosomes, and highlight recent discoveries on the forward trafficking of nascent receptors.