Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
41
pubmed:dateCreated
1995-12-4
pubmed:abstractText
Inherited forms of prion disease have been linked to mutations in the gene encoding PrP, a neuronal and glial protein that is attached to the plasma membrane by a glycosyl-phosphatidylinositol (GPI) anchor. One familial form of Creutzfeldt-Jakob disease is associated with a mutant PrP containing six additional octapeptide repeats. We report here our analysis of cultured Chinese hamster ovary cells expressing a murine homologue of this mutant PrP. We find that, like wild-type PrP, the mutant protein is glycosylated, GPI-anchored, and expressed on the cell surface. Surprisingly, however, cleavage of the GPI anchor using phosphatidylinositol-specific phospholipase C fails to release the mutant PrP from the surface of intact cells, suggesting that it has an additional mode of membrane attachment. The phospholipase-treated protein is hydrophobic, since it partitions into the detergent phase of Triton X-114 lysates; and it is tightly membrane-associated, since it is not extractable in carbonate buffer at pH 11.5. Whether membrane attachment of the mutant PrP involves integration of the polypeptide into the lipid bilayer, self-association, or binding to other membrane proteins remains to be determined. Our results suggest that alterations in the membrane association of PrP may be an important feature of prion diseases.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
13
pubmed:volume
270
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
24589-97
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:7592679-Amino Acid Sequence, pubmed-meshheading:7592679-Animals, pubmed-meshheading:7592679-Antibodies, pubmed-meshheading:7592679-Base Sequence, pubmed-meshheading:7592679-CHO Cells, pubmed-meshheading:7592679-Cell Membrane, pubmed-meshheading:7592679-Creutzfeldt-Jakob Syndrome, pubmed-meshheading:7592679-Cricetinae, pubmed-meshheading:7592679-DNA Primers, pubmed-meshheading:7592679-Glycosylation, pubmed-meshheading:7592679-Glycosylphosphatidylinositols, pubmed-meshheading:7592679-Humans, pubmed-meshheading:7592679-Lipid Bilayers, pubmed-meshheading:7592679-Mice, pubmed-meshheading:7592679-Molecular Sequence Data, pubmed-meshheading:7592679-Mutagenesis, pubmed-meshheading:7592679-Mutation, pubmed-meshheading:7592679-Peptide Fragments, pubmed-meshheading:7592679-Phosphatidylinositol Diacylglycerol-Lyase, pubmed-meshheading:7592679-Phosphoinositide Phospholipase C, pubmed-meshheading:7592679-Phosphoric Diester Hydrolases, pubmed-meshheading:7592679-Polymerase Chain Reaction, pubmed-meshheading:7592679-Prions, pubmed-meshheading:7592679-Recombinant Proteins, pubmed-meshheading:7592679-Transfection
pubmed:year
1995
pubmed:articleTitle
A mutant prion protein displays an aberrant membrane association when expressed in cultured cells.
pubmed:affiliation
Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't