A Novel Endocytic Recycling Signal Distinguishes Biological Responses of Trk Neurotrophin Receptors

Chen ZY, Ieraci A, Tanowitz M and Lee FS
Source: Mol Biol Cell
Publication Date: (2005)
Issue: 16(12): 5761-5772
Research Area:
Cells used in publication:
Neuron, hippo/cortical, rat
Species: rat
Tissue Origin: brain
Nucleofector® I/II/2b
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 (TrkA, TrkB) traverse divergent endocytic pathways after binding to their respective ligands (NGF, BDNF). 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 PI3 kinase/Akt signaling, as well as survival responses, as 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.