DOI: 10.1073/pnas.94.6.2333. COOH-terminal sequence of the cellular prion protein directs subcellular trafficking and controls conversion into the scrapie isoform

COOH-terminal sequence of the cellular prion protein directs subcellular trafficking and controls conversion into the scrapie isoform

10.1073/pnas.94.6.2333

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Efficient formation of scrapie isoform of prion protein (PrPSc) requires targeting PrPScby glycophosphatidyl inositol (GPI) anchors to caveolae-like domains (CLDs). Redirecting the cellular isoform of prion protein (PrPC) to clathrin-coated pits by creating chimeric PrP molecules with four different COOH-terminal transmembrane domains prevented the formation of PrPSc. To determine if these COOH-terminal transmembrane segments prevented PrPCfrom refolding into PrPScby altering the structure of the polypeptide, we fused the 28-aa COOH termini from the Qa protein. Two COOH-terminal Qa segments differing by a single residue direct the transmembrane protein to clathrin-coated pits or the GPI form to CLDs; PrPScwas formed from GPI-anchored PrPCbut not from transmembrane PrPC. Our findings argue that PrPScformation is restricted to a specific subcellular compartment and as such, it is likely to involve auxiliary macromolecules found within CLDs.

Bibliography

Kaneko, K., Vey, M., Scott, M., Pilkuhn, S., Cohen, F. E., & Prusiner, S. B. (1997). COOH-terminal sequence of the cellular prion protein directs subcellular trafficking and controls conversion into theâscrapieâisoform. Proceedings of the National Academy of Sciences, 94(6), 2333â2338.

Authors 6

Kiyotoshi Kaneko (first)
Martin Vey (additional)
Michael Scott (additional)
Susanne Pilkuhn (additional)
Fred E. Cohen (additional)
Stanley B. Prusiner (additional)

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:44 a.m.)
Deposited	2 years, 4 months ago (April 22, 2023, 8:33 a.m.)
Indexed	1 month, 2 weeks ago (July 14, 2025, 11:16 p.m.)
Issued	28 years, 5 months ago (March 18, 1997)
Published	28 years, 5 months ago (March 18, 1997)
Published Online	28 years, 5 months ago (March 18, 1997)
Published Print	28 years, 5 months ago (March 18, 1997)

Funders 0

None

BibTeX

@article{Kaneko_1997, title={COOH-terminal sequence of the cellular prion protein directs subcellular trafficking and controls conversion into the scrapie isoform}, volume={94}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.94.6.2333}, DOI={10.1073/pnas.94.6.2333}, number={6}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Kaneko, Kiyotoshi and Vey, Martin and Scott, Michael and Pilkuhn, Susanne and Cohen, Fred E. and Prusiner, Stanley B.}, year={1997}, month=mar, pages={2333–2338} }

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