title: Trafficking of PrPc to mitochondrial raft-like microdomains during cell apoptosis.
abstract: The cellular form of prion protein (PrP (c)) is a highly conserved cell surface GPI-anchored glycoprotein that was identified in cholesterol-enriched, detergent-resistant microdomains, named "rafts." The association with these specialized portions of the cell plasma membrane is required for conversion of PrP (c) to the transmissible spongiform encephalopathy-associated protease-resistant isoform. Usually, PrP (c) is reported to be a plasma membrane protein, however several studies have revealed PrP (c) as an interacting protein mainly with the membrane/organelles, as well as with cytoskeleton network. Recent lines of evidence indicated its association with ER lipid raft-like microdomains for a correct folding of PrP (c), as well as for the export of the protein to the Golgi and proper glycosylation. During cell apoptosis, PrP (c) can undergo intracellular re-localization, via ER-mitochondria associated membranes (MAM) and microtubular network, to mitochondrial raft-like microdomains, where it induced the loss of mitochondrial membrane potential and citochrome c release, after a contained raise of calcium concentration. We suggest that PrP (c) may play a role in the multimolecular signaling complex associated with cell apoptosis Lipid rafts and their components may, thus, be investigated as pharmacological targets of interest, introducing a novel and innovative task in modern pharmacology, i.e., the development of glycosphingolipid targeted drugs.
authors: Department of Experimental Medicine, Sapienza University, Rome, Italy. maurizio.sorice@uniroma1.it
authors: Maurizio
authors: M
authors: Sorice
authors: Vincenzo
authors: V
authors: Mattei
authors: Vincenzo
authors: V
authors: Tasciotti
authors: Valeria
authors: V
authors: Manganelli
authors: Tina
authors: T
authors: Garofalo
authors: Roberta
authors: R
authors: Misasi
mesh_terms: D000818:Animals; D017209:Apoptosis; D006801:Humans; D021962:Membrane Microdomains / Q000378:metabolism* / Q000473:pathology; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D018621:PrPC Proteins / Q000378:metabolism*; D017096:Prion Diseases / Q000378:metabolism* / Q000473:pathology; D021381:Protein Transport
chemical_list: D018621:PrPC Proteins