NR ATHX
AU Laffont-Proust,I.; Faucheux,B.A.; Hässig,R.; Sazdovitch,V.; Simon,S.; Grassi,J.; Hauw,J.J.; Moya,K.L.; Haik,S.
TI The N-terminal cleavage of cellular prion protein in the human brain
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Cell Biology of PrPc and PrPsc CELL-29
PT Konferenz-Poster
AB Human brain cellular prion protein is cleaved within its highly conserved domain at amino acid 110/111-112. This cleavage generates a highly stable C-terminal fragment (C1) anchored to the plasma membrane. We examined the relative abundance of holo- and truncated cellular prion protein in human cerebral cortex from non-CJD patients (n=23) by Western blotting. We found important inter-individual variations in the proportion of the C-terminal fragment. We found no artifactual in vitro truncation of PrPc in our experimental conditions. To study possible sources for the striking variability in PrPc cleavage we examined human brain samples that varied in terms of age and postmortem interval. The results showed no obvious variation in C1 related to age. When the results were analyzed with respect to postmortem interval, there was no significant correlation with this variable. Thus, neither age nor postmortem interval explain the large variability observed in C1 amount. To further examine mechanisms that may contribute to the cleavage of PrPc, we examined the proteases TACE and ADAM10 which have been reported to cleave PrPc in vitro in our series of human samples. We found no association between active form of TACE and presence of C1 fragment. However, interestingly, our results show that high amount of C1 is associated with the presence of the active ADAM10 suggesting this zinc metalloprotease as a candidate for the cleavage of cellular prion protein in the human brain. Support: GIS Prion.
IN Die Autoren fanden bei 23 nicht an CJK erkrankten Menschen große Unterschiede hinsichtlich des Anteils der Prionproteine, bei denen der Aminoterminus abgespalten war. Diese Variabilität hatte nichts mit dem Alter der Patienten, dem zeitlichen Abstand zwischen Tod und Probennahme oder mit der Aktivität der TACE-Protease zu tun. Einen Zusammenhang fanden sie aber zwischen der Aktivität der Zink-Metallo-Protease ADAM10 und dem Anteil gespaltener Prionproteine.
AD Isabelle Laffont-Proust, Raymonde Hässig, Kenneth L. Moya1, CEA-CNRS URA2210, F. Joliot Hospital, 4, place du Général Leclerc, F-91406 Orsay, France; Baptiste A. Faucheux, Véronique Sazdovitch, Jean-Jacques Hauw, Stéphane Haïk, INSERM Avenir team "Human prion diseases", IFR70, Neuropathology, Salpêtrière Hospital, F-75013 Paris, France; Stéphanie Simon, Jacques Grassi, Pharmacology and Immunology department, CEA/Saclay, F-91191 Gif-sur-Yvette, France
SP englisch
PO Deutschland