title: Abnormal plasma membrane properties and functions in prion-infected cell lines.
abstract: A long trail of evidence indicates that the formation of PrPSc or its accumulation causes the neuronal dysfunction and clinical features of prion diseases. The results of our current line of studies argue that the main neuropathological and clinical features of prion diseases are explained by altered ion channel function secondary to decreased plasma membrane fluidity. This kind of mechanism has the potential to functionally disconnect neuronal networks and cause neuronal vacuolation. Our laboratory is currently focusing its investigations on pathogenic mechanisms that have the potential to link the formation of PrPSc with plasma membrane abnormalities in prion diseases. In summary, the first hypothesis suggests that the conversion of PrPC to PrPSc affects plasma membrane fluidity directly, which secondarily alters the properties and functions of its components. In contrast, the second hypothesis argues that PrPSc accumulation alters the ability of chaperones to correctly fold plasma-membrane proteins during their synthesis, which directly affects the properties of nascent proteins and secondarily affects membrane fluidity. Our current investigations are attempting to determine which of these mechanisms are plausible and, then, which is primary.
authors.affiliation: Department of Pathology, University of California at San Francisco 94143, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: DeArmond
authors.forename: Y
authors.initials: Y
authors.lastname: Qiu
authors.forename: K
authors.initials: K
authors.lastname: Wong
authors.forename: R
authors.initials: R
authors.lastname: Nixon
authors.forename: W
authors.initials: W
authors.lastname: Hyun
authors.forename: S B
authors.initials: SB
authors.lastname: Prusiner
authors.forename: W C
authors.initials: WC
authors.lastname: Mobley
mesh_terms: D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D007293:Inosine Triphosphate / Q000378:metabolism; D008560:Membrane Fluidity / Q000502:physiology; D017096:Prion Diseases / Q000378:metabolism / Q000473:pathology*; D011328:Prions / Q000378:metabolism
chemical_list: D011328:Prions; D007293:Inosine Triphosphate