The N-terminal cleavage of cellular prion protein in the human brain.
Human brain cellular prion protein (PrP(c)) is cleaved within its highly conserved domain at amino acid 110/111/112. This cleavage generates a highly stable C-terminal fragment (C1). We examined the relative abundance of holo- and truncated PrP(c) in human cerebral cortex and we found important inter-individual variations in the proportion of C1. Neither age nor postmortem interval explain the large variability observed in C1 amount. Interestingly, our results show that high levels of C1 are associated with the presence of the active ADAM 10 suggesting this zinc metalloprotease as a candidate for the cleavage of PrP(c) in the human brain.
Laffont-Proust
Isabelle
I
INSERM Avenir Team - Human Prion Diseases, IFR70, Neuropathology, Salpêtrière Hospital, F-75013 Paris, France.
Faucheux
Baptiste A
BA
Hässig
Raymonde
R
Sazdovitch
Véronique
V
Simon
Stéphanie
S
Grassi
Jacques
J
Hauw
Jean-Jacques
JJ
Moya
Kenneth L
KL
Haïk
Stéphane
S
D051722:ADAM Proteins / Q000378:metabolism*; D000072197:ADAM10 Protein; D000367:Age Factors; D053829:Amyloid Precursor Protein Secretases; D002540:Cerebral Cortex / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D010084:Oxidation-Reduction; D018621:PrPC Proteins / Q000378:metabolism*; D017434:Protein Structure, Tertiary
D008565:Membrane Proteins; D018621:PrPC Proteins; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human