Differential endocytic sorting of p75NTR and TrkA in response to NGF: A role for late endosomes in TrkA trafficking

Smita Saxena, Charles L. Howe, José M. Cosgaya, Pascal Steiner, Harald Hirling, Jonah R. Chan, Joachim Weis, Alex Krüttgen

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

NGF binds to two receptors, p75NTR and TrkA. The endosomal trafficking of receptors is of emerging importance for the understanding of their signaling. We compared the endocytic trafficking of the two NGF receptors in PC12 cells. Both p75NTR and TrkA were internalized in response to NGF and colocalized with early endosomes. However, surprisingly, the subsequent endosomal trafficking paths of both NGF receptors diverged: whereas p75NTR recycled back to the surface, TrkA moved to late endosomes and underwent lysosomal degradation. By performing subcellular fractionations of NGF stimulated PC12 cells, tyrosine-phosphorylated TrkA was recovered in fractions corresponding to late endosomes. This implicates these organelles as novel endosomal NGF signaling platforms. Furthermore, the trafficking of NGF receptors could be manipulated by pharmacological means. Disrupting p75NTR recycling diminished TrkA activation in response to low concentrations of NGF, demonstrating a functional role for the recycling of p75NTR.

Original languageEnglish (US)
Pages (from-to)571-587
Number of pages17
JournalMolecular and Cellular Neuroscience
Volume28
Issue number3
DOIs
StatePublished - Mar 2005

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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