High-resolution fractionation of signaling endosomes containing different receptors

Gretchen McCaffrey, Jonathan Welker, Jessica Scott, Louise van der Salm, Mark L. Grimes

Research output: Contribution to journalArticlepeer-review

Abstract

Receptor endocytosis is regulated by ligand binding, and receptors may signal after endocytosis in signaling endosomes. We hypothesized that signaling endosomes containing different types of receptors may be distinct from one another and have different physical characteristics. To test this hypothesis, we developed a high-resolution organelle fractionation method based on mass and density, optimized to resolve endosomes from other organelles. Three different types of receptors undergoing ligand-induced endocytosis were localized predominately in endosomes that were resolved from one another using this method. Endosomes containing activated receptor tyrosine kinases (RTKs), TrkA and EGFR, were similar to one another. Endosomes containing p75 NTR (in the tumor necrosis receptor superfamily) and PAC1 (a G-protein-coupled receptor) were distinct from each other and from RTK endosomes. Receptor-specific endosomes may direct the intracellular location and duration of signal transduction pathways to dictate response to signals and determine cell fate.

Original languageEnglish
Pages (from-to)938-950
Number of pages13
JournalTraffic
Volume10
Issue number7
DOIs
StatePublished - 2009

Keywords

  • Endosome
  • Nerve growth factor
  • Organelle fractionation
  • Receptor
  • Signal transduction

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