Abstract
Subcellular pathways and accumulation of internalized radiolabeled neurotrophins NGF, BDNF, and NT-3 were examined in retinal ganglion cells (RGCs) of chick embryos by using quantitative electron microscopic autoradiography. All three neurotrophins accumulated in endosomes and multivesicular bodies. BDNF and NGF also concentrated at the plasma membrane, whereas NT-3 accumulated transiently in the Golgi system. The enhanced targeting of NT-3 to the Golgi system correlated with the anterograde axonal transport of this neurotrophin. Anterograde transport of NT-3, but not its internalization, was significantly attenuated by the tyrosine kinase (trk) inhibitor K252a. Abolishment of trk activity with K252a shifted NT-3 (and BDNF) away from the Golgi system and into a lysosomal pathway, indicating that trk activity regulated sorting of the ligand-receptor complex. Cross-linking of neurotrophins and immunoprecipitation with antibodies to the neurotrophin receptors p75, trkA, trkB, and trkC showed that the large majority of exogenous, receptor-bound NT-3 was bound to trkC in RGC somata, but during anterograde transport in the optic nerve most receptor-bound NT-3 was associated with p75, and after arrival and release in the optic tectum transferred to presumably postsynaptic trkC. These results reveal remarkable and unexpected differences in the intracellular pathways and fates of different neurotrophins within the same cell type. They provide first evidence for an endocytic pathway of internalized neurotrophic factors via the Golgi system before anterograde transport and transcytosis. The results challenge the belief that after internalization all neurotrophins are rapidly degraded in lysosomes.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.