Signaling Endosomes

When neurotrophin receptors at the axon terminal are activated by their cognate ligands, signals are propagated to the neuronal cell body to regulate survival and differentiation. It has been thought that retrograde transport of endocytic vesicles containing such receptor-ligand complexes transmit these signals. Howe et al. report that clathrin-coated vesicles (CCVs) were induced in PC12 cells and dorsal root ganglia neurons upon treatment with nerve growth factor (NGF). Ultrastructural and biochemical characterization of isolated CCVs showed that NGF stimulated the recruitment of clathrin to neuronal membranes and that NGF bound to its receptor, TrkA, was present in the CCVs. Inhibition of TrkA abolished movement of NGFs into CCVs. However, CCVs accounted for approximately 50% of the total NGF internalized, indicating that other mechanisms are at work. Increased association of activated proteins of the Ras-Erk pathway with NGF-induced CCVs was also observed indicating that these signaling endosomes could serve as a platform for propagating signals through this pathway. The authors propose that TrkA activation may induce the local formation of CCVs and that further recruitment of signaling components contributes to downstream signaling events. C. L. Howe, J. S. Valletta, A. S. Rusnak, W. C. Mobley, NGF signaling from clathrin-coated vesicles: Evidence that signaling endosomes serve as a platform for the Ras-MAPK pathway. Neuron 32 , 801-814 (2001). [Online Journal]