title: VE-cadherin-derived cell-penetrating peptide, pVEC, with carrier functions.
abstract: Cell-penetrating peptides, CPPs, have been shown to translocate into living cells by a receptor-independent mechanism and to carry macromolecules over the plasma membrane. This article reports studies of the internalization of pVEC, an 18-amino acid-long peptide derived from the murine sequence of the cell adhesion molecule vascular endothelial cadherin, amino acids 615-632. Fluorophore-labeled pVEC entered four different cell lines tested: human aortic endothelial cells, brain capillary endothelial cells, Bowes melanoma cells, and murine brain endothelial cells. In order to evaluate the translocation efficiency of pVEC, we performed a side-by-side comparison with penetratin, a well-characterized CPP. The cellular uptake of pVEC was highest for murine brain endothelial cells. All cell lines tested contained equal or slightly higher concentrations of pVEC than penetratin. pVEC mainly accumulated in nuclear structures but was also found throughout the cells. Furthermore, pVEC functioned as a transporter of both a hexameric peptide nucleic acid molecule of 1.7 kDa and a 67-kDa protein, streptavidin-FITC, and cellular uptake of fluorophore-labeled pVEC took place at 4 degrees C, suggesting a nonendocytotic mechanism of translocation. In conclusion, our results indicate that pVEC is efficiently and rapidly taken up into cells and functions as a potent carrier peptide.
authors.affiliation: Department of Neurochemistry and Neurotoxicology, Stockholm University, Stockholm, S-106 91, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Elmquist
authors.forename: M
authors.initials: M
authors.lastname: Lindgren
authors.forename: T
authors.initials: T
authors.lastname: Bartfai
authors.lastname: Langel U
mesh_terms: D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD; D001011:Aorta / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D057846:Cell-Penetrating Peptides; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism; D005456:Fluorescent Dyes / Q000494:pharmacology; D006801:Humans; D013058:Mass Spectrometry; D008545:Melanoma / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D008956:Models, Chemical; D008969:Molecular Sequence Data; D010452:Peptide Biosynthesis; D010455:Peptides / Q000737:chemistry*; D013997:Time Factors; D014407:Tumor Cells, Cultured; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D002352:Carrier Proteins; D057846:Cell-Penetrating Peptides; D005456:Fluorescent Dyes; D010455:Peptides; D000099152:Cadherin 5; C437783:pVEC peptide; C414409:penetratin