NR AXNU
AU Haigh,C.L.; Boland,M.; Lewis,V.; Hill,A.F.; Lawson,V.; Masters,C.L.; Collins,S.J.
TI Investigation into the Role of PrPc Cleavage in Intracellular Signalling and Disease Pathogenesis
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.54
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
Background: The cellular prion protein (PrPc) is known to undergo two cleavage events (termed alpha and beta cleavage). These events are influenced by cellular factors such as copper and oxidative stress. The cell membrane is known to have an important role in the transduction of signals from the extracellular environment into the cell. This, combined with the association of the N-terminal PrPc cleavage fragments with intracellular signalling, may suggest that PrPc is involved in cellular survival responses by the activation of signal transduction cascades. The cleavage event that has been termed beta cleavage is associated with disease, and several disease associated mutations have been linked with altered cellular cleavage. The effect of this altered cleavage on the cell or the susceptibility to infection is unknown.
Aim(s)/Objective(s): This project aims to investigate the role of the N-terminal cleavage of PrPc in intracellular signalling, and establish if aberrant processing is involved in disease pathogenesis either by transduction of abnormal signals or by altering susceptibility to infection.
Methods; The aims have been addressed using a combination of cell culture methods, including cellular signalling and infectivity assays, and recombinant protein techniques.
Results: Perturbation of the membrane environment by agents that alter membrane fluidity has been shown to influence the cleavage profile of both human and mouse PrPc when expressed in the RK13 cell line. PrPc from the different species is processed differently both at the basal level and in response to insult. Investigation into these effects on cellular signalling pathways finds that cellular signalling proteins are altered, in both the amount of total protein and level of activation, differently for the mouse and human PrPcs.
Discussion: The membrane environment is critical for the transduction of signals into the cell from external stimuli. The finding that modification of the membrane
environment influences the cleavage profile of PrPc and affects cellular signalling proteins suggests the involvement of PrPc processing in signal transduction.
AD C. Haigh, M. Boland, V. Lewis,V. Lawson, Colin L. Masters, Steven J. Collins, The University of Melbourne, Australia; A. Hill, The University of Melbourne, Australia
SP englisch
PO Schottland
EA pdf-Datei und Poster (Postertitel: Perturbation of the Cell Membrane Alters PrP Cleavage and Intracellular Signalling)