NGF signaling in sensory neurons: evidence that early endosomes carry NGF retrograde signals.
Target-derived NGF promotes the phenotypic maintenance of mature dorsal root ganglion (DRG) nociceptive neurons. Here, we provide in vivo and in vitro evidence for the presence within DRG neurons of endosomes containing NGF, activated TrkA, and signaling proteins of the Rap1/Erk1/2, p38MAPK, and PI3K/Akt pathways. Signaling endosomes were shown to be retrogradely transported in the isolated sciatic nerve in vitro. NGF injection in the peripheral target of DRG neurons increased the retrograde transport of p-Erk1/2, p-p38, and pAkt in these membranes. Conversely, NGF antibody injections decreased the retrograde transport of p-Erk1/2 and p-p38. Our results are evidence that signaling endosomes, with the characteristics of early endosomes, convey NGF signals from the target of nociceptive neurons to their cell bodies.
Delcroix
Jean-Dominique
JD
Department of Neurology and Neurological Sciences, Stanford University, Stanford 94305, USA. jdd@stanford.edu
Valletta
Janice S
JS
Wu
Chengbiao
C
Hunt
Stephen J
SJ
Kowal
Anthony S
AS
Mobley
William C
WC
D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D002478:Cells, Cultured; D011992:Endosomes / Q000378:metabolism* / Q000648:ultrastructure; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D020932:Nerve Growth Factor / Q000502:physiology*; D009475:Neurons, Afferent / Q000502:physiology* / Q000648:ultrastructure; D009924:Organ Culture Techniques; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020917:Receptor, trkA / Q000502:physiology; D012584:Sciatic Nerve / Q000166:cytology / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D020932:Nerve Growth Factor; D020917:Receptor, trkA; D020928:Mitogen-Activated Protein Kinases