N-terminal peptides from unprocessed prion proteins enter cells by macropinocytosis

Mazin Magzoub, Staffan Sandgren, Pontus Lundberg, Kamila Oglecka, Johanna Lilja, Anders Wittrup, L. E. Göran Eriksson, Ülo Langel, Mattias Belting, Astrid Gräslund

Research output: Contribution to journalArticle

Abstract

A peptide derived from the N-terminus of the unprocessed bovine prion protein (bPrPp), incorporating the hydrophobic signal sequence (residues 1-24) and a basic domain (KKRPKP, residues 25-30), internalizes into mammalian cells, even when coupled to a sizeable cargo, and therefore functions as a cell-penetrating peptide (CPP). Confocal microscopy and co-localization studies indicate that the internalization of bPrPp is mainly through macropinocytosis, a fluid-phase endocytosis process, initiated by binding to cell-surface proteoglycans. Electron microscopy studies show internalized bPrPp-DNA-gold complexes residing in endosomal vesicles. bPrPp induces expression of a complexed luciferase-encoding DNA plasmid, demonstrating the peptide's ability to transport the cargo across the endosomal membrane and into the cytosol and nucleus. The novel CPP activity of the unprocessed N-terminal domain of PrP could be important for the retrotranslocation of partly processed PrP and for PrP trafficking inside or between cells, with implications for the infectivity associated with prion diseases.

Original languageEnglish (US)
Pages (from-to)379-385
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume348
Issue number2
DOIs
StatePublished - Sep 22 2006

Keywords

  • Cell-penetrating peptide
  • Endocytosis
  • Macropinocytosis
  • N-terminus
  • Prion protein
  • Proteoglycan

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Magzoub, M., Sandgren, S., Lundberg, P., Oglecka, K., Lilja, J., Wittrup, A., Göran Eriksson, L. E., Langel, Ü., Belting, M., & Gräslund, A. (2006). N-terminal peptides from unprocessed prion proteins enter cells by macropinocytosis. Biochemical and Biophysical Research Communications, 348(2), 379-385. https://doi.org/10.1016/j.bbrc.2006.07.065