Linked Life Data

12837762

Source:http://linkedlifedata.com/resource/pubmed/id/12837762

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
37
pubmed:dateCreated
2003-9-8
pubmed:abstractText
Protein transduction domains (PTDs) are short basic peptide sequences present in many cellular and viral proteins that mediate translocation across cellular membranes. PTDs have become widely used as tools for the delivery of high Mr polypeptides, polynucleotides, or nanoparticles to cells in culture; and even the transfer of cargo molecules to the tissue of live animals has been reported. These cell-permeable peptides are functional when fused in-frame to recombinant polypeptides or when chemically coupled to their cargo. The mechanism responsible for PTD-mediated membrane translocation is controversially discussed and may vary among the various PTDs reported in the literature. Thus direct physical interaction with membrane lipids resulting in vectorial delivery to cells has been proposed for the Antennapedia (Antp) PTD, whereas uptake by the retroviral TAT (transactivator of transcription) protein PTD seems to require cell surface-expressed glycosaminoglycans. The view that PTD-mediated cellular uptake is energy-independent has been dismissed recently as an artifact resulting from fixation of cells. The data reported here agree with and further extend this work. They support the idea that certain PTDs promote cellular uptake via endocytosis and require the expression of negatively charged glycosaminoglycans on the surface of the target cells. Uptake of Antp PTD conjugates or peptide-derivatized liposomes was blocked by heparan sulfate proteoglycans, whereas TAT-mediated uptake was inhibited by both heparin and dextran sulfate. Mutant cells defective for glycosaminoglycan synthesis showed dramatically reduced Antp- or TAT-mediated transmembrane transport confirming the role of these complex polysaccharides in PTD-mediated cellular uptake. The fact that PTDs selectively interact with distinct glycosaminoglycan species has implications for therapeutic applications and may allow targeting of selective tissues that differ in their surface-expressed glycosaminoglycan patterns.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
12
pubmed:volume
278
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
35109-14
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12837762-Amino Acid Sequence, pubmed-meshheading:12837762-Animals, pubmed-meshheading:12837762-Antennapedia Homeodomain Protein, pubmed-meshheading:12837762-Binding Sites, pubmed-meshheading:12837762-Cell Membrane, pubmed-meshheading:12837762-Dextran Sulfate, pubmed-meshheading:12837762-Endocytosis, pubmed-meshheading:12837762-Gene Products, tat, pubmed-meshheading:12837762-Glycosaminoglycans, pubmed-meshheading:12837762-HeLa Cells, pubmed-meshheading:12837762-Heparin, pubmed-meshheading:12837762-Homeodomain Proteins, pubmed-meshheading:12837762-Humans, pubmed-meshheading:12837762-Lysosomes, pubmed-meshheading:12837762-Melanoma, Experimental, pubmed-meshheading:12837762-Membrane Lipids, pubmed-meshheading:12837762-Mice, pubmed-meshheading:12837762-Molecular Sequence Data, pubmed-meshheading:12837762-Nuclear Proteins, pubmed-meshheading:12837762-Peptide Fragments, pubmed-meshheading:12837762-Protein Transport, pubmed-meshheading:12837762-Receptors, Transferrin, pubmed-meshheading:12837762-Transcription Factors, pubmed-meshheading:12837762-Tumor Cells, Cultured
pubmed:year
2003
pubmed:articleTitle
Antennapedia and HIV transactivator of transcription (TAT) "protein transduction domains" promote endocytosis of high molecular weight cargo upon binding to cell surface glycosaminoglycans.
pubmed:affiliation
Biomolecular Research, Paul Scherrer Institut, CH-5232 Villigen, Switzerland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't