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Titolo:
Sorting of internalized neurotrophins into an endocytic transcytosis pathway via the Golgi system: Ultrastructural analysis in retinal ganglion cells
Autore:
Butowt, R; von Bartheld, CS;
Indirizzi:
Univ Nevada, Sch Med, Dept Physiol & Cell Biol, Reno, NV 89557 USA Univ Nevada Reno NV USA 89557 ept Physiol & Cell Biol, Reno, NV 89557 USA
Titolo Testata:
JOURNAL OF NEUROSCIENCE
fascicolo: 22, volume: 21, anno: 2001,
pagine: 8915 - 8930
SICI:
0270-6474(20011115)21:22<8915:SOINIA>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
NERVE GROWTH-FACTOR; RETROGRADE AXONAL-TRANSPORT; PC12 PHEOCHROMOCYTOMA CELLS; RAT SYMPATHETIC NEURONS; HIGH-AFFINITY RECEPTORS; HIPPOCAMPAL-NEURONS; VISUAL-SYSTEM; CHICK-EMBRYOS; ANTEROGRADE TRANSPORT; SIGNAL-TRANSDUCTION;
Keywords:
anterograde transport; BDNF; NT-3; NGF; trkB; trkC; p75 neurotrophin receptor; neurotrophic factor; visual system; internalization; degradation; K252a; Golgi; lysosome; sorting; retina;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
107
Recensione:
Indirizzi per estratti:
Indirizzo: von Bartheld, CS Univ Nevada, Sch Med, Dept Physiol & Cell Biol, Mailstop 352, Reno, NV 89557 USA Univ Nevada Mailstop 352 Reno NV USA 89557 , NV 89557 USA
Citazione:
R. Butowt e C.S. von Bartheld, "Sorting of internalized neurotrophins into an endocytic transcytosis pathway via the Golgi system: Ultrastructural analysis in retinal ganglion cells", J NEUROSC, 21(22), 2001, pp. 8915-8930

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, wassignificantly 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 withinthe same cell type. They provide first evidence for an endocytic pathway of internalized neurotrophic factors via the Golgi system before anterogradetransport and transcytosis. The results challenge the belief that after internalization all neurotrophins are rapidly degraded in lysosomes.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/11/20 alle ore 12:42:05