NGF Signals through TrkA to Increase Clathrin at the Plasma Membrane and Enhance Clathrin-Mediated Membrane Trafficking

摘要: Neurotrophin (NT) signals may be moved from axon terminals to neuron cell bodies via signaling endosomes-organelles in which NTs continue bound their activated receptors. Suggesting that clathrin-coated membranes serve as one source of endosomes, earlier studies we showed nerve growth factor (NGF) treatment increased clathrin at the plasma membrane and resulted colocalization with TrkA, receptor tyrosine kinase for NGF. Strikingly, however, also noted most puncta surface NGF-treated cells did not colocalize raising possibility NGF induces a general increase formation. To explore this further, examined distribution NGF- BDNF-treated cells. PC12 robustly redistributed adaptor protein AP2 heavy chain (CHC) membranes. Using confocal epifluorescence microscopy, well biochemical assays, redistribution attributable activation TrkA. Significantly, signaled through TrkA induce an clathrin-mediated trafficking, revealed endocytosis transferrin. In BDNF hippocampal neurons, these findings represent physiologically significant response NTs. We conclude NT increases formation trafficking speculate effect contributes trophic actions internalization receptors other proteins are present