Cellular uptake of arginine-rich peptides: roles for macropinocytosis and actin rearrangement

Nakase, Ikuhiko, Niwa, Miki, Takeuchi, Toshihide, Sonomura, Kazuhiro, Ueda, Kunihiro, Simpson, Jeremy C., Jones, Arwyn Tomos ORCID: https://orcid.org/0000-0003-2781-8905, Sugiura, Yukio and Futaki, Shiroh 2004. Cellular uptake of arginine-rich peptides: roles for macropinocytosis and actin rearrangement. Molecular Therapy 10 (6) , pp. 1011-22. 10.1016/j.ymthe.2004.08.010

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Abstract

The use of membrane-permeable peptides as carrier vectors for the intracellular delivery of various proteins and macromolecules for modifying cellular function is well documented. Arginine-rich peptides, including those derived from human immunodeficiency virus 1 Tat protein, are among the representative classes of these vectors. The internalization mechanism of these vector peptides and their protein conjugates was previously regarded as separate from endocytosis, but more recent reevaluations have concluded that endocytosis is involved in their internalization. In this report, we show that the uptake of octa-arginine (R8) peptide by HeLa cells was significantly suppressed by the macropinocytosis inhibitor ethylisopropylamiloride (EIPA) and the F-actin polymerization inhibitor cytochalasin D, suggesting a role for macropinocytosis in the uptake of the peptide. In agreement with this we observed that treatment of the cells with R8 peptide induced significant rearrangement of the actin cytoskeleton. The internalization efficiency and contribution of macropinocytosis were also observed to have a dependency on the chain length of the oligoarginine peptides. Uptake of penetratin, another representative peptide carrier, was less sensitive to EIPA and penetratin did not have such distinct effects on actin localization. The above observations suggest that penetratin and R8 peptides have distinct internalization mechanisms.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy
Subjects:	R Medicine > RS Pharmacy and materia medica
Uncontrolled Keywords:	HIV-1 Tat, arginine-rich peptides, internalization, protein delivery, protein transduction, cell-permeable peptide, penetratin, macropinocytosis, actin rearrangement
Publisher:	American Society for Gene & Cell Therapy
ISSN:	1525-0024
Last Modified:	17 Oct 2022 08:44
URI:	https://orca.cardiff.ac.uk/id/eprint/928

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