NR ATCA
AU Butowt,R.; Abdelraheim,S.R.; Brown,D.R.; von Bartheld,C.S.
TI Anterograde axonal transport of the exogenous cellular isoform of prion protein in the chick visual system
QU Molecular and Cellular Neurosciences 2006 Jan; 31(1): 97-108
PT journal article
AB The cellular isoform of endogenous, newly synthesized prion protein (PrPc) can be transported by axons in the anterograde direction. To determine whether a mechanism exists for secreted PrPc to be internalized and then axonally transported, we analyzed internalization and anterograde axonal transport of radiolabeled recombinant PrPc after its intraocular injection in chick embryos. Internalization and axonal transport of exogenous PrPc to the midbrain by retinal ganglion cells (RGCs) is efficient, saturable and likely receptor-mediated. Ultrastructural quantitative localization of radiolabeled PrPc within RGC soma showed significant labeling of vesicular/endosomal compartments and much less labeling present over the Golgi apparatus and lysosomes, which indicates slow degradation of exogenous PrPc in this system. These data show that a mechanism exists to internalize a secreted form of PrPc and then to axonally transport such PrPc in an anterograde direction. This may provide an additional, novel mechanism for prion protein to spread among neurons.
IN Die Autoren markierten normales, zelluläres Prionprotein radioaktiv und injizierten es in Augen lebender Hühnerembryonen. Danach beobachteten sie, dass die Ganglionzellen der Netzhaut das Prionprotein effektiv aufnahmen und es durch den Sehnerv ins Gehirn transportierten. Dabei fiel auf, dass bei hohen Konzentrationen ein Sättigungseffekt auftritt. Dies spricht für eine Rezeptor-vermittelte Aufnahme des Prionproteins. Innerhalb der Nervenzellen fand man die radioaktiv markierten Prionproteine besonders in Endosomen und anderen Vesikeln. In Golgi-Apparat und Lysosomen fand man wesentlich weniger Prionprotein, welches also in diesen Neuronen nur langsam abgebaut zu werden scheint.
MH Animals; Axonal Transport/*physiology; Axons/*physiology; Chick Embryo; Prions/genetics/*metabolism; Recombinant Proteins/metabolism; Research Support, N.I.H., Extramural; Retina/embryology; Retinal Ganglion Cells/physiology; Vision/*physiology
AD Rafal Butowt (rafalbutowt@yahoo.com), Christopher S. von Bartheld, Department of Physiology and Cell Biology, Mail Stop 352, University of Nevada School of Medicine, Reno, NV-89557, USA; Salama Abdelraheim, David R. Brown, Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK
SP englisch
PO USA