Combinatorial Targeting and Discovery of Ligand-Receptors in Organelles of Mammalian Cells

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Combinatorial Targeting and Discovery of Ligand-Receptors in Organelles of Mammalian Cells

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Title: Combinatorial Targeting and Discovery of Ligand-Receptors in Organelles of Mammalian Cells
Author: Rangel, Roberto; Guzman-Rojas, Liliana; le Roux, Lucia G.; Staquicini, Fernanda I.; Hosoya, Hitomi; Barbu, E. Magda; Ozawa, Michael G.; Nie, Jing; Langley, Robert R.; Sage, E. Helene; Koivunen, Erkki; Gelovani, Juri G.; Lobb, Roy R.; Pasqualini, Renata; Arap, Wadih; Sidman, Richard Leon; Dunner, Kenneth, Jr.

Note: Order does not necessarily reflect citation order of authors.

Citation: Rangel, Roberto, Liliana Guzman-Rojas, Lucia G. le Roux, Fernanda I. Staquicini, Hitomi Hosoya, E. Magda Barbu, Michael G. Ozawa, et al. 2012. Combinatorial targeting and discovery of ligand-receptors in organelles of mammalian cells. Nature Communications 3:788.
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Abstract: Phage display screening allows the study of functional protein–protein interactions at the cell surface, but investigating intracellular organelles remains a challenge. Here we introduce internalizing-phage libraries to identify clones that enter mammalian cells through a receptor-independent mechanism and target-specific organelles as a tool to select ligand peptides and identify their intracellular receptors. We demonstrate that penetratin, an antennapedia-derived peptide, can be displayed on the phage envelope and mediate receptor-independent uptake of internalizing phage into cells. We also show that an internalizing-phage construct displaying an established mitochondria-specific localization signal targets mitochondria, and that an internalizing-phage random peptide library selects for peptide motifs that localize to different intracellular compartments. As a proof-of-concept, we demonstrate that one such peptide, if chemically fused to penetratin, is internalized receptor-independently, localizes to mitochondria, and promotes cell death. This combinatorial platform technology has potential applications in cell biology and drug development.
Published Version: doi:10.1038/ncomms1773
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3337985/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10357579
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