TY - JOUR T1 - Evidence of Presynaptic Location and Function of the Prion Protein JF - The Journal of Neuroscience JO - J. Neurosci. SP - 8866 LP - 8875 DO - 10.1523/JNEUROSCI.19-20-08866.1999 VL - 19 IS - 20 AU - Jochen Herms AU - Tobias Tings AU - Stefan Gall AU - Axel Madlung AU - Armin Giese AU - Heike Siebert AU - Peter Schürmann AU - Otto Windl AU - Nils Brose AU - Hans Kretzschmar Y1 - 1999/10/15 UR - http://www.jneurosci.org/content/19/20/8866.abstract N2 - 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 H2O2, 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 H2O2 was found to correlate with the amount of PrPC expression in the presynaptic neuron in cerebellar slice preparations from wild-type, Prnp0/0, 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. ER -