Cell Biology of the Prion Protein

Gorodinsky, A.; Lehmann, Sylvain; Moulder, Krista L.; Shyng, Show Ling

doi:10.1007/978-3-642-60983-1_7

Cited by 34 publications

(26 citation statements)

References 39 publications

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“…An important piece of information that may shed light on the functional interaction of PrP C and copper is how the metal affects the cellular localization and trafficking of PrP C . We have shown previously that PrP C is constitutively endocytosed from the plasma membrane via clathrin-coated pits and transits an early endosomal compartment before being recycled back to the cell surface (25)(26)(27)(28). We report here that copper has a dramatic effect on this cycle.…”

mentioning

confidence: 72%

“…Because PrP C is attached to the cell surface by a glycosyl-phosphatidylinositol anchor, it lacks a cytoplasmic domain that could bind directly to the intracellular components of coated pits. We have therefore postulated the existence of a transmembrane receptor whose extracellular domain binds PrP C via its N-terminal region and whose cytoplasmic domain contains signals for interacting with adapter molecules and clathrin (27,28).…”

Section: Copper Stimulates Endocytosis Of the Prion Protein 33109mentioning

confidence: 99%

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Copper Stimulates Endocytosis of the Prion Protein

Pauly¹,

Harris

1998

Journal of Biological Chemistry

559

450

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confidence: 72%

Section: Copper Stimulates Endocytosis Of the Prion Protein 33109mentioning

confidence: 99%

Copper Stimulates Endocytosis of the Prion Protein

Pauly¹,

Harris

1998

Journal of Biological Chemistry

559

450

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“…The normal or cellular prion protein (PrP C ) 4 is predominantly a cell surface protein that is sensitive to proteases and is soluble in non-ionic detergents (1)(2)(3)(4). In humans, the posttranslational modified, full-length PrP C is made of 209 amino acids (residues 23-231), which include two sites of N-glycosylation, and carries a glycosylphosphatidylinositol (GPI) anchor (Fig.…”

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Characterization of the Prion Protein in Human Urine

Dagdanova

Ilchenko

Notari

et al. 2010

Journal of Biological Chemistry

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The presence of the prion protein (PrP) in normal human urine is controversial and currently inconclusive. This issue has taken a special relevance because prion infectivity has been demonstrated in urine of animals carrying experimental or naturally occurring prion diseases, but the actual presence and tissue origin of the infectious prion have not been determined. We used immunoprecipitation, one-and two-dimensional electrophoresis, and mass spectrometry to prove definitely the presence of PrP in human urine and its post-translational modifications. We show that urinary PrP (uPrP) is truncated mainly at residue 112 but also at other residues up to 122. This truncation makes uPrP undetectable with some commonly used antibodies to PrP. uPrP is glycosylated and carries an anchor which, at variance with that of cellular PrP, lacks the inositol-associated phospholipid moiety, indicating that uPrP is probably shed from the cell surface. The detailed characterization of uPrP reported here definitely proves the presence of PrP in human urine and will help determine the origin of prion infectivity in urine.

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“…Normally, PrP is a cell-surface N-linked glycoprotein that is widely expressed and particularly abundant in the brain, although its function is unknown (7). A 22-aa N-terminal signal peptide directs PrP into the endoplasmic reticulum (ER) cotranslationally.…”

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Wild-type PrP and a mutant associated with prion disease are subject to retrograde transport and proteasome degradation

Lindquist

2001

Proc. Natl. Acad. Sci. U.S.A.

271

237

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The cytoplasm seems to provide an environment that favors conversion of the prion protein (PrP) to a form with the physical characteristics of the PrP Sc conformation, which is associated with transmissible spongiform encephalopathies. However, it is not clear whether PrP would ever exist in the cytoplasm under normal circumstances. We report that PrP accumulates in the cytoplasm when proteasome activity is compromised. The accumulated PrP seems to have been subjected to the normal proteolytic cleavage events associated with N-and C-terminal processing in the endoplasmic reticulum, suggesting that it arrives in the cytoplasm through retrograde transport. In the cytoplasm, PrP forms aggregates, often in association with Hsc70. With prolonged incubation, these aggregates accumulate in an ''aggresome''-like state, surrounding the centrosome. A mutant (D177N), which is associated with a heritable and transmissible form of the spongiform encephalopathies, is less efficiently trafficked to the surface than wild-type PrP and accumulates in the cytoplasm even without proteasome inhibition. These results demonstrate that PrP can accumulate in the cytoplasm and is likely to enter this compartment through normal protein quality-control pathways. Its potential to accumulate in the cytoplasm has implications for pathogenesis.

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Cell Biology of the Prion Protein

Cited by 34 publications

References 39 publications

Copper Stimulates Endocytosis of the Prion Protein

Copper Stimulates Endocytosis of the Prion Protein

Characterization of the Prion Protein in Human Urine

Wild-type PrP and a mutant associated with prion disease are subject to retrograde transport and proteasome degradation

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