Recruitment of cellular prion protein to mitochondrial raft-like microdomains contributes to apoptosis execution.
We examined the possibility that cellular prion protein (PrP(C)) plays a role in the receptor-mediated apoptotic pathway. We first found that CD95/Fas triggering induced a redistribution of PrP(C) to the mitochondria of T lymphoblastoid CEM cells via a mechanism that brings into play microtubular network integrity and function. In particular, we demonstrated that PrP(C) was redistributed to raft-like microdomains at the mitochondrial membrane, as well as at endoplasmic reticulum-mitochondria-associated membranes. Our in vitro experiments also demonstrated that, although PrP(C) had such an effect on mitochondria, it induced the loss of mitochondrial membrane potential and cytochrome c release only after a contained rise of calcium concentration. Finally, the involvement of PrP(C) in apoptosis execution was also analyzed in PrP(C)-small interfering RNA-transfected cells, which were found to be significantly less susceptible to CD95/Fas-induced apoptosis. Taken together, these results suggest that PrP(C) might play a role in the complex multimolecular signaling associated with CD95/Fas receptor-mediated apoptosis.
Laboratory of Experimental Medicine and Environmental Pathology, Sabina Universitas, 02100 Rieti, Italy.
Vincenzo
V
Mattei
Paola
P
Matarrese
Tina
T
Garofalo
Antonella
A
Tinari
Lucrezia
L
Gambardella
Laura
L
Ciarlo
Valeria
V
Manganelli
Vincenzo
V
Tasciotti
Roberta
R
Misasi
Walter
W
Malorni
Maurizio
M
Sorice
D017209:Apoptosis / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism; D006801:Humans; D021962:Membrane Microdomains / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000235:genetics / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000378:metabolism*; D018621:PrPC Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism*
C491901:FAS protein, human; D018621:PrPC Proteins; D034741:RNA, Small Interfering; D019014:fas Receptor; D045304:Cytochromes c; D002118:Calcium