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

Mazin Magzoub, Staffan Sandgren, Pontus Lundberg, Kamila Oglecka, Johanna Welch, Anders Wittrup, L. E. Goran Eriksson, Ulo Langel, Mattias Belting, Astrid Graslund

Research output: Contribution to journalArticlepeer-review


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. (c) 2006 Elsevier Inc. All rights reserved.
Original languageEnglish
Pages (from-to)379-385
JournalBiochemical and Biophysical Research Communications
Issue number2
Publication statusPublished - 2006

Subject classification (UKÄ)

  • Biological Sciences

Free keywords

  • proteoglycan
  • macropinocytosis
  • endocytosis
  • cell-penetrating peptide
  • prion protein
  • N-terminus


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