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, Chemistry
    Journal of controlled release : official journal of the Controlled Release Society
  • 2005
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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.
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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