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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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. (c) 2006 Elsevier Inc. All rights reserved.

Detaljer

Författare
  • Mazin Magzoub
  • Staffan Sandgren
  • Pontus Lundberg
  • Kamila Oglecka
  • Johanna Welch
  • Anders Wittrup
  • L. E. Goran Eriksson
  • Ulo Langel
  • Mattias Belting
  • Astrid Graslund
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Biologiska vetenskaper

Nyckelord

Originalspråkengelska
Sidor (från-till)379-385
TidskriftBiochemical and Biophysical Research Communications
Volym348
Utgivningsnummer2
StatusPublished - 2006
PublikationskategoriForskning
Peer review utfördJa