A prion protein cycles between the cell surface and an endocytic compartment in cultured neuroblastoma cells

Show-Ling Shyng, Mary T. Huber, David A. Harris

Research output: Contribution to journalArticle

248 Citations (Scopus)

Abstract

The prion protein (PrPC) is a glycolipid-anchored, cell surface protein of unknown function, a posttranslationally modified isoform of which has been implicated in the pathogenesis of spongiform encephalopathies in man and animals. We report here the novel observation that chPrP, the chicken homologue of mammalian PrPC, constitutively cycles between the cell surface and an endocytic compartment with a transit time of ∼60 min, as demonstrated by surface iodination and immunofluorescence microscopy. Most (>95%) of the internalized protein is returned to the cell surface intact, and the remainder is proteolytically cleaved within a highly conserved region in the NH2-terminal half of the molecule. Pulse-chase labeling experiments indicate that while this cleavage is slow, with a rate of ∼1%/h, the COOH-terminal fragment produced is stable and accumulates on the cell surface for as long as 24 h. The cleavage is likely to take place in an acidified endocytic compartment, since it is reduced by lysosomotropic amines and inhibitors of lysosomal proteases. Our results raise the possibility that chPrP, and perhaps other PrPCs, function as cell surface receptors, and they suggest cellular pathways that might be involved in the generation of the pathogenic isoform.

Original languageEnglish (US)
Pages (from-to)15922-15928
Number of pages7
JournalJournal of Biological Chemistry
Volume268
Issue number21
StatePublished - Jul 25 1993
Externally publishedYes

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Neuroblastoma
Cultured Cells
Cell Cycle
Protein Isoforms
Halogenation
Glycolipids
Cell Surface Receptors
Brain Diseases
Protease Inhibitors
Fluorescence Microscopy
Amines
PrPC Proteins
Chickens
Membrane Proteins
Observation
Labeling
Microscopic examination
Animals
Proteins
Peptide Hydrolases

ASJC Scopus subject areas

  • Biochemistry

Cite this

A prion protein cycles between the cell surface and an endocytic compartment in cultured neuroblastoma cells. / Shyng, Show-Ling; Huber, Mary T.; Harris, David A.

In: Journal of Biological Chemistry, Vol. 268, No. 21, 25.07.1993, p. 15922-15928.

Research output: Contribution to journalArticle

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