Transducible TAT-HA fusogenic peptide enhances escape of TAT-fusion proteins after lipid raft macropinocytosis

@article{Wadia2004TransducibleTF,
  title={Transducible TAT-HA fusogenic peptide enhances escape of TAT-fusion proteins after lipid raft macropinocytosis},
  author={Jehangir S. Wadia and Radu V Stan and Steven F Dowdy},
  journal={Nature Medicine},
  year={2004},
  volume={10},
  pages={310-315}
}
The TAT protein transduction domain (PTD) has been used to deliver a wide variety of biologically active cargo for the treatment of multiple preclinical disease models, including cancer and stroke. However, the mechanism of transduction remains unknown. Because of the TAT PTD's strong cell-surface binding, early assumptions regarding cellular uptake suggested a direct penetration mechanism across the lipid bilayer by a temperature- and energy-independent process. Here we show, using a… 
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Cationic TAT peptide transduction domain enters cells by macropinocytosis.
  • I. Kaplan, J. Wadia, S. Dowdy
  • Biology, Medicine
    Journal of controlled release : official journal of the Controlled Release Society
  • 2005
TLDR
Observations provide a solid scientific basis for the development of novel biologically active transducible anticancer PTD peptide therapeutics.
Internalization of novel non-viral vector TAT-streptavidin into human cells
TLDR
This study demonstrates that TAT-SA-PPAA is a potential non-viral vector to be utilized in protein therapeutics to deliver biotinylated molecules both into cytoplasm and nucleus of human cells.
Endosome disruption enhances the functional nuclear delivery of Tat-fusion proteins.
TLDR
This work indicates that an inadequate intracellular trafficking is the main factor limiting the efficiency of protein cargo delivery using Tat and suggests that Tat-fusion proteins enter via the endosomal pathway, circumvent lysosomal degradation, and are then sequestered in the periphery of the nucleus.
Protein transduction in human cells is enhanced by cell-penetrating peptides fused with an endosomolytic HA2 sequence
TLDR
It is demonstrated that a CPP tagged with an endosomolytic fusion peptide derived from the influenza virus hemagglutinin-2 (HA2) remarkably enhances the cytosolic delivery of proteins in human A549 cells, suggesting that the CPP-HA2 tag could be an efficient and safe carrier that overcomes endosomal entrapment of delivered therapeutic drugs.
Improved cytosolic translocation and tumor-killing activity of Tat-shepherdin conjugates mediated by co-treatment with Tat-fused endosome-disruptive HA2 peptide.
TLDR
It is proposed that this HA2Tat-mediated cytosolic delivery technique led to enhanced cytotoxicity of Tat-fused anti-cancer peptides, specifically shepherdin and it is demonstrated that this is a useful method for the delivery of therapeutic macromolecules into the cytosol.
The mechanism of TAT-mediated cellular transduction: Role of glycans and Rab GTPases
TLDR
The roles of glycans expressed on the cell surface and small GTPases in the process of macropinocytotic uptake of transducible peptides and proteins are elucidated to support a model whereby TAT induces membrane ruffling and macrop inocytosis via Rac1 and Rab34, independent of its binding to glycans.
Transcellular protein transduction using the Tat protein of HIV-1.
TLDR
The Tat protein of HIV-1 is a powerful transactivator of gene expression that interacts with a structured RNA sequence at the 5' end of the viral mRNA, and mediates their efficient cellular internalization and can be thus utilized for transcellular protein transduction.
Single Particle Tracking Confirms That Multivalent Tat Protein Transduction Domain-induced Heparan Sulfate Proteoglycan Cross-linkage Activates Rac1 for Internalization*
TLDR
The successful visualization and tracking of TatP molecular kinetics on the cell surface with 7-nm spatial precision using quantum dots is reported, clarifying the initial binding mechanism and demonstrating the importance of Tatp valence for strong surface binding and signal transduction.
Tat-tetanus toxin fragment C: a novel protein delivery vector and its use with photochemical internalization
TLDR
The combined use of the Tat-TTC delivery vector with PCI led to both enhancement of neural cell type specific delivery to an endosomal target, followed by the option of efficient release to the cytosol.
Cellular Uptake of Unconjugated TAT Peptide Involves Clathrin-dependent Endocytosis and Heparan Sulfate Receptors*
TLDR
It is demonstrated that the entry of TAT peptide into different primary cells is ATP and temperature-dependent, indicating the involvement of endocytosis, and suggested that unconjugated peptide might follow endocytic pathways different from those utilized by T AT peptide conjugated to different proteins.
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