Retrogradely Transported TrkA Endosomes Signal Locally within Dendrites to Maintain Sympathetic Neuron Synapses

Publication date: 4 April 2017
Source:Cell Reports, Volume 19, Issue 1
Author(s): Kathryn M. Lehigh, Katherine M. West, David D. Ginty
Sympathetic neurons require NGF from their target fields for survival, axonal target innervation, dendritic growth and formation, and maintenance of synaptic inputs from preganglionic neurons. Target-derived NGF signals are propagated retrogradely, from distal axons to somata of sympathetic neurons via TrkA signaling endosomes. We report that a subset of TrkA endosomes that are transported from distal axons to cell bodies translocate into dendrites, where they are signaling competent and move bidirectionally, in close proximity to synaptic protein clusters. Using a strategy for spatially confined inhibition of TrkA kinase activity, we found that distal-axon-derived TrkA signaling endosomes are necessary within sympathetic neuron dendrites for maintenance of synapses. Thus, TrkA signaling endosomes have unique functions in different cellular compartments. Moreover, target-derived NGF mediates circuit formation and synapse maintenance through TrkA endosome signaling within dendrites to promote aggregation of postsynaptic protein complexes.

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Teaser

Lehigh et al. follow TrkA endosome dynamics in distinct cellular locales using live-cell imaging. Chemical genetics and drug-loaded microspheres are used to spatially and specifically inhibit TrkA kinase activity, demonstrating that distal-axon-derived TrkA signaling endosomes within the somatodendritic compartment in vivo and within dendrites in vitro mediate synapse maintenance.


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