title: Retrogradely Transported TrkA Endosomes Signal Locally within Dendrites to Maintain Sympathetic Neuron Synapses.
abstract: 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.
authors.affiliation: Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA; Neuroscience Training Program, Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Lehigh
authors.affiliation: Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: West
authors.affiliation: Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA. Electronic address: david_ginty@hms.harvard.edu.
authors.forename: David D
authors.initials: DD
authors.lastname: Ginty
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008863:Microspheres; D020932:Nerve Growth Factor / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D061848:Optical Imaging; D010766:Phosphorylation; D011134:Polysaccharides / Q000378:metabolism; D020917:Receptor, trkA / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013564:Sympathetic Nervous System / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D059008:Time-Lapse Imaging
chemical_list: D011134:Polysaccharides; C010491:neurotropin; D020932:Nerve Growth Factor; D020917:Receptor, trkA
keywords: NFG; PLGA microspheres; TrkA; dendrites; microfluidic chambers; neurotrophin; ptosis; signaling endosome; sympathetic neuron; synapse formation