NGF signaling from clathrin-coated vesicles: evidence that signaling endosomes serve as a platform for the Ras-MAPK pathway.
The target-derived neurotrophic factor "nerve growth factor" (NGF) signals through TrkA to promote the survival, differentiation, and maintenance of neurons. How the NGF signal in axon terminals is conveyed to the cell body is unknown. The "signaling endosome hypothesis" envisions that NGF-TrkA complexes are internalized at the axon terminal and retrogradely transported to the cell body. Following NGF treatment, we found that clathrin-coated vesicles contained NGF bound to TrkA together with activated signaling proteins of the Ras-MAP kinase pathway. Evidence that these vesicles could signal was their ability in vitro to activate Elk, a downstream target of Erk1/2. Our results point to the existence of a population of signaling endosomes derived from clathrin-coated membranes in NGF-treated cells.
Howe
C L
CL
Department of Neurology, Stanford University Medical Center, 1201 Welch Road, MSLS P211, Stanford, CA 94305, USA. howe.charles@mayo.edu
Valletta
J S
JS
Rusnak
A S
AS
Mobley
W C
WC
D000818:Animals; D002478:Cells, Cultured; D022163:Clathrin-Coated Vesicles / Q000502:physiology*; D011992:Endosomes / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D020932:Nerve Growth Factor / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D016716:PC12 Cells; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020917:Receptor, trkA / Q000378:metabolism; D018631:ras Proteins / Q000502:physiology*
D020932:Nerve Growth Factor; D020917:Receptor, trkA; D020928:Mitogen-Activated Protein Kinases; D018631:ras Proteins