Evidence in support of signaling endosome-based retrograde survival of sympathetic neurons.
The mechanism by which target-derived Nerve Growth Factor (NGF) signaling is propagated retrogradely, over extremely long distances, to cell bodies to support survival of neurons is unclear. Here we show that survival of sympathetic neurons supported by NGF on distal axons requires the kinase activity of the NGF receptor, TrkA, in both distal axons and cell bodies. In contrast, disruption of TrkA activity exclusively in proximal axonal segments affects neither retrograde NGF-TrkA signaling in cell bodies nor neuronal survival. Ligand-receptor internalization is necessary for survival of neurons supported by NGF on distal axons. Furthermore, antibody neutralization experiments indicate that retrogradely transported NGF, within cell bodies, is critical for neuronal survival but not for growth of distal axons. Taken together, our results indicate that retrogradely transported NGF-TrkA complexes promote sympathetic neuron survival.
Ye
Haihong
H
Department of Neuroscience, Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Kuruvilla
Rejji
R
Zweifel
Larry S
LS
Ginty
David D
DD
D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D002451:Cell Compartmentation / Q000502:physiology; D002470:Cell Survival; D002478:Cells, Cultured; D011992:Endosomes / Q000378:metabolism* / Q000648:ultrastructure; D020932:Nerve Growth Factor / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D020917:Receptor, trkA / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013564:Sympathetic Nervous System / Q000166:cytology / Q000378:metabolism
D020932:Nerve Growth Factor; D020917:Receptor, trkA