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

Magzoub, Mazin; Sandgren, Staffan LU ; Lundberg, Pontus; Oglecka, Kamila; Welch, Johanna LU ; Wittrup, Anders LU ; Eriksson, L. E. Goran; Langel, Ulo; Belting, Mattias LU and Graslund, Astrid (2006) In Biochemical and Biophysical Research Communications 348(2). p.379-385
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
proteoglycan, macropinocytosis, endocytosis, cell-penetrating peptide, prion protein, N-terminus
in
Biochemical and Biophysical Research Communications
volume
348
issue
2
pages
379 - 385
publisher
Elsevier
external identifiers
  • wos:000240275000008
  • pmid:16893522
  • scopus:33746911543
ISSN
1090-2104
DOI
10.1016/j.bbrc.2006.07.065
language
English
LU publication?
yes
id
540f300e-e486-4b09-913e-25c4c838ffce (old id 394854)
date added to LUP
2007-10-09 14:03:26
date last changed
2018-07-01 04:17:45
@article{540f300e-e486-4b09-913e-25c4c838ffce,
  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.},
  author       = {Magzoub, Mazin and Sandgren, Staffan and Lundberg, Pontus and Oglecka, Kamila and Welch, Johanna and Wittrup, Anders and Eriksson, L. E. Goran and Langel, Ulo and Belting, Mattias and Graslund, Astrid},
  issn         = {1090-2104},
  keyword      = {proteoglycan,macropinocytosis,endocytosis,cell-penetrating peptide,prion protein,N-terminus},
  language     = {eng},
  number       = {2},
  pages        = {379--385},
  publisher    = {Elsevier},
  series       = {Biochemical and Biophysical Research Communications},
  title        = {N-terminal peptides from unprocessed prion proteins enter cells by macropinocytosis},
  url          = {http://dx.doi.org/10.1016/j.bbrc.2006.07.065},
  volume       = {348},
  year         = {2006},
}