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, w
The cellular form of prion protein (PrPC) 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 PrPC to the transmissible spongiform encephalopathy-associated protease-resistant isoform. Usually, PrPC is reported to be a plasma membrane protein, however several studies have revealed PrPC 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 PrPC, as well as for the export of the protein to the Golgi and proper glycosylation. During cell apoptosis, PrPC 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 cytochrome c release, after a contained raise of calcium concentration. We suggest that PrPC may play a role in the multi-molecular 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.
Trafficking of PrPC to mitochondrial raft-like microdomains during cell apoptosis / Sorice, Maurizio; Vincenzo, Mattei; Tasciotti, Vincenzo; Manganelli, Valeria; Garofalo, Tina; Misasi, Roberta. - In: PRION. - ISSN 1933-6896. - 6:4(2012), pp. 354-358. [10.4161/pri.20479]
Trafficking of PrPC to mitochondrial raft-like microdomains during cell apoptosis
SORICE, Maurizio;TASCIOTTI, VINCENZO;MANGANELLI, VALERIA;GAROFALO, TINA;MISASI, Roberta
2012
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, wI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.