NGF signaling from clathrin-coated vesicles: Evidence that signaling endosomes serve as a platform for the Ras-MAPK pathway

Charles L. Howe, Janice S. Valletta, Alex S. Rusnak, William C. Mobley

Research output: Contribution to journalArticle

272 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)801-814
Number of pages14
Issue number5
StatePublished - Dec 6 2001


ASJC Scopus subject areas

  • Neuroscience(all)

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