|SCHMITZ, MATTHIAS - Goettingen University|
|GREIS, CATHARINA - Goettingen University|
|OTTIS, PHILLIP - Heinrich-Heine University|
|Silva, Christopher - Chris|
|SCHULZ-SCHAEFFER, WALTER - Georg August University|
|WREDE, ARNE - Heinrich-Heine University|
|KOPPE, KATHARINA - Heinrich-Heine University|
|REQUEAN, JESUS - University Of Santiago De Compostela|
Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 4/4/2014
Publication Date: 6/16/2014
Publication URL: http://acselb-529643017.us-west-2.elb.amazonaws.com/chem/248nm/program/view.php
Citation: Schmitz, M., Greis, C., Ottis, P., Silva, C.J., Schulz-Schaeffer, W.J., Wrede, A., Koppe, K., Requean, J.R. 2014. The physiological role of the normal cellular prion protein (PrPC) [abstract]. Meeting Abstract. Current Topics in Biological Chemistry. Paper No. 113.
Technical Abstract: The normal cellular prion protein (PrPC) is a highly conserved protein expressed by the prnp gene. It is an essential substrate for the propagation of transmissible spongiform encephalopathies (TSEs), but its natural function remains uncertain. Mice, genetically engineered to be devoid of the prnp gene (PrP0/0) and therefore unable to express PrPC, appear to develop normally and are able to reproduce. This indicates that the gene, though highly conserved, is not essential for viability. Transgenic mouse, tissue and cell-based models were used to better understand the physiological role of PrPC. Wildtype (WT) and PrP0/0 mice were subjected to a series of standard behavioral tests to detect phenotypic differences. Tissues from WT and PrP0/0 mice were studied at the physiological level. Biochemical differences in mouse derived tissues were examined by mass spectrometry. PrP0/0 mice show age-dependent behavioral deficits in memory performance, associative learning, basal anxiety and nest building behavior. Four neurofilament (NF) proteins increased in aged WT mice but not in aged PrP0/0 mice. Another five proteins were found differentially abundant in older (18 month) WT as compared to PrP0/0 mice. A reduction in NF-H phosphorylation in both PrP0/0 mice and in PrPC deficient cells was observed. The expression of Fyn and phospho-Fyn, a potential regulator for NF phosphorylation, was associated with PrPC ablation. The number of '-tubulin III-positive neurons in the hippocampus was diminished in PrP0/0 mice relative to WT mice. These data indicate that PrPC plays an important role in cytoskeletal organization, brain function, and age-related neuroprotection. Our work represents the first direct biochemical link between these proteins and the observed behavioral phenotypes.