Cellular uptake [correction of utake] of the Tat peptide: an endocytosis mechanism following ionic interactions.
The cellular delivery of various biological compounds has recently been improved by conjugating them to short peptides known as protein transduction domains or cell penetrating peptides. These peptides include Tat, Antennapedia and arginine-rich peptides. The common feature of these peptides is their highly cationic nature. Up to now, the cellular uptake of about 50 different peptides and proteins coupled to Tat or Antennapedia peptides has been reported. The ability to deliver molecules into cells is not limited to peptide moieties, since oligonucleotides, peptide nucleic acids or other low molecular weight entities have been successfully internalized. Moreover, most of these examples have been accompanied by the expected biological response. More surprisingly, the uptake of large structures such as liposomes, phages, nanoparticles or adenoviruses has also been documented. Indeed the mechanism by which these very different entities could enter cells following a putative common pathway appeared more and more intriguing after each new reported example of cellular uptake mediated by these peptides. After a long period of uncertainty regarding the mechanism of entry, data from several groups now argue for an energy-dependent process of entry. The entry of most of these molecules is likely to be inhibited by low temperature incubation or in the presence of various drugs applied to inhibit the energy-dependent pathway of cell entry. Moreover, the binding of the highly cationic Tat peptide to various anionic membrane components probably initiates the first step of the cell internalization process.
Vives
Eric
E
Université de Montpellier II, Institut de Génétique Moléculaire, CNRS UMR-5124, 1919 route de Mende, 34293 Montpellier, France. vives@igms.cnrs-mop.fr
D000818:Animals; D001693:Biological Transport, Active; D004705:Endocytosis / Q000502:physiology*; D015696:Gene Products, tat / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D008565:Membrane Proteins; D010455:Peptides; D054322:tat Gene Products, Human Immunodeficiency Virus