A novel endocytic recycling signal distinguishes biological responses of Trk neurotrophin receptors. Academic Article uri icon

Overview

abstract

  • Endocytic trafficking of signaling receptors to alternate intracellular pathways has been shown to lead to diverse biological consequences. In this study, we report that two neurotrophin receptors (tropomyosin-related kinase TrkA and TrkB) traverse divergent endocytic pathways after binding to their respective ligands (nerve growth factor and brain-derived neurotrophic factor). We provide evidence that TrkA receptors in neurosecretory cells and neurons predominantly recycle back to the cell surface in a ligand-dependent manner. We have identified a specific sequence in the TrkA juxtamembrane region, which is distinct from that in TrkB receptors, and is both necessary and sufficient for rapid recycling of internalized receptors. Conversely, TrkB receptors are predominantly sorted to the degradative pathway. Transplantation of the TrkA recycling sequence into TrkB receptors reroutes the TrkB receptor to the recycling pathway. Finally, we link these divergent trafficking pathways to alternate biological responses. On prolonged neurotrophin treatment, TrkA receptors produce prolonged activation of phosphatidylinositol 3-kinase/Akt signaling as well as survival responses, compared with TrkB receptors. These results indicate that TrkA receptors, which predominantly recycle in signal-dependent manner, have unique biological properties dictated by its specific endocytic trafficking itinerary.

publication date

  • October 5, 2005

Research

keywords

  • Endocytosis
  • Receptor, trkA
  • Signal Transduction

Identity

PubMed Central ID

  • PMC1289419

Scopus Document Identifier

  • 28644440548

Digital Object Identifier (DOI)

  • 10.1091/mbc.e05-07-0651

PubMed ID

  • 16207814

Additional Document Info

volume

  • 16

issue

  • 12