The N-terminal domain of a glycolipid-anchored prion protein is essential for its endocytosis via clathrin-coated pits

Show-Ling Shyng, K. L. Moulder, A. Lesko, D. A. Harris

Research output: Contribution to journalArticle

142 Citations (Scopus)

Abstract

The cellular priori protein (PrP(C)) is a glycolipid-anchored protein that is involved in the pathogenesis of fatal spongiform encephalopathies. We have shown previously that, in contrast to several other glycolipid-anchored proteins, chPrP, the chicken homologue of mammalian PrP(C), is endocytosed via clathrin-coated pits in cultured neuroblastoma cells, as well as in embryonic neurons and glia (Shyng, S.-L., Heuser, J. E., and Harris, D. A. (1994) J. Cell Biol. 125, 1239-1250). In this study, we have determined that the N-terminal half of the chPrP polypeptide chain is essential for its endocytosis. Deletions within this region reduce the amount of chPrP internalized, as measured by surface iodination or biotinylation, and decrease its concentration in clathrin-coated pits, as determined by quantitative electron microscopic immunogold labeling. Mouse PrP, as well as two mouse PrP/chPrP chimeras, are internalized as efficiently as chPrP, suggesting that conserved features of secondary and tertiary structure are involved in interaction with the endocytic machinery. Our results indicate that the ectodomain of a protein can contain endocytic targeting information, and they strongly support a model in which the polypeptide chain of PrP(C) binds to the extracellular domain of a transmembrane protein that contains a coated pit localization signal in its cytoplasmic tail.

Original languageEnglish (US)
Pages (from-to)14793-14800
Number of pages8
JournalJournal of Biological Chemistry
Volume270
Issue number24
DOIs
StatePublished - 1995
Externally publishedYes

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Clathrin
Glycolipids
Endocytosis
Proteins
Biotinylation
Peptides
Halogenation
Brain Diseases
Protein C
Neuroblastoma
Neuroglia
Labeling
Neurons
Machinery
Tail
Chickens
Cultured Cells
Electrons
Prion Proteins
Prions

ASJC Scopus subject areas

  • Biochemistry

Cite this

The N-terminal domain of a glycolipid-anchored prion protein is essential for its endocytosis via clathrin-coated pits. / Shyng, Show-Ling; Moulder, K. L.; Lesko, A.; Harris, D. A.

In: Journal of Biological Chemistry, Vol. 270, No. 24, 1995, p. 14793-14800.

Research output: Contribution to journalArticle

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