NR AFIE
AU Herms,J.W.; Tings,T.; Gall,S.; Madlung,A.; Giese,A.; Siebert,H.; Schurmann,P.; Windl,O.; Brose,N.; Kretzschmar,H.A.
TI Evidence of presynaptic location and function of the prion protein
QU Journal of Neuroscience 1999 Oct 15; 19(20): 8866-75
PT journal article
AB The prion protein (PrPc) is a copper-binding protein of unknown function that plays an important role in the etiology of transmissible spongiform encephalopathies. Using morphological techniques and synaptosomal fractionation methods, we show that PrPc is predominantly localized to synaptic membranes. Atomic absorption spectroscopy was used to identify PrPc-related changes in the synaptosomal copper concentration in transgenic mouse lines. The synaptic transmission in the presence of H(2)O(2), which is known to be decomposed to highly reactive hydroxyl radicals in the presence of iron or copper and to alter synaptic activity, was studied in these animals. The response of synaptic activity to H(2)O(2) was found to correlate with the amount of PrPc expression in the presynaptic neuron in cerebellar slice preparations from wild-type, Prnp(0/0), and PrP gene-reconstituted transgenic mice. Thus, our data gives strong evidence for the predominantly synaptic location of PrPc, its involvement in the regulation of the presynaptic copper concentration, and synaptic activity in defined conditions.
MH Amyloid/genetics/metabolism; Animal; Cerebellum/metabolism; Copper/metabolism; Hydrogen Peroxide/pharmacology; Mice; Mice, Inbred C57BL; Mice, Transgenic/genetics; Neural Inhibition/drug effects; Osmolar Concentration; PrPc Proteins/genetics/metabolism; Presynaptic Terminals/*metabolism; Prions/genetics/metabolism/*physiology; Protein Precursors/genetics/metabolism; Retina/metabolism; Support, Non-U.S. Gov't; Synaptic Transmission/drug effects; Tissue Distribution
AD Department of Neuropathology, Georg-August Universität Göttingen, 37075 Göttingen, Germany.
SP englisch
PO USA