Document Detail

Recruitment of cellular prion protein to mitochondrial raft-like microdomains contributes to apoptosis execution.
MedLine Citation:
PMID:  22031292     Owner:  NLM     Status:  MEDLINE    
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.
Vincenzo Mattei; Paola Matarrese; Tina Garofalo; Antonella Tinari; Lucrezia Gambardella; Laura Ciarlo; Valeria Manganelli; Vincenzo Tasciotti; Roberta Misasi; Walter Malorni; Maurizio Sorice
Publication Detail:
Type:  Journal Article     Date:  2011-10-26
Journal Detail:
Title:  Molecular biology of the cell     Volume:  22     ISSN:  1939-4586     ISO Abbreviation:  Mol. Biol. Cell     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-15     Completed Date:  2012-07-30     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  9201390     Medline TA:  Mol Biol Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4842-53     Citation Subset:  IM    
Laboratory of Experimental Medicine and Environmental Pathology, Sabina Universitas, 02100 Rieti, Italy.
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MeSH Terms
Antigens, CD95 / genetics,  metabolism*
Apoptosis / physiology*
Calcium / metabolism
Cell Line, Tumor
Cytochromes c / genetics,  metabolism
Membrane Microdomains / genetics,  metabolism*
Microtubules / genetics,  metabolism
Mitochondrial Membranes / metabolism*
PrPC Proteins / genetics,  metabolism*
RNA, Small Interfering / genetics
Signal Transduction / physiology*
Reg. No./Substance:
0/Antigens, CD95; 0/FAS protein, human; 0/PrPC Proteins; 0/RNA, Small Interfering; 7440-70-2/Calcium; 9007-43-6/Cytochromes c

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