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

By I. Nakase, M. Niwa, T. Takeuchi, K. Sonomura, N. Kawabata, Y. Koike, M. Takehashi, Seigo Tanaka, K. Ueda, J. Simpson and 3 more. Molecular Therapy, 2004

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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.

Subfields: Genetics, Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/2dac295fef0d06c9438936de6319ba9f67eade48

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Citations in the corpus

Uptake Pathways and Subsequent Intracellular Trafficking in Nonviral Gene Delivery (2006, background): “Recent reports have demonstrated that the uptake of the TAT peptide and its cargos occurs by macropinocytosis (Kaplan et al., 2005; Nakase et al., 2004; Wadia et al., 2004).”
Cell‐penetrating peptides: 20 years later, where do we stand? (2013, background): “Macropinocytosis: Macropinocytosis was demonstrated to be implicated in the internalization of polyarginines [135], and to a much less extent of penetratin.”
Heparan sulfate proteoglycans mediate internalization and propagation of specific proteopathic seeds (2013, background): “(2007) beta-Sheet structured beta-amyloid(1-40) perturbs phosphatidylcholine model membranes.”
Twenty years of cell-penetrating peptides: from molecular mechanisms to therapeutics (2009, neutral): “Ever since, the mechanism of many CPPs has re-examined and reported to be mediated by endocytosis (Lundberg and Johansson, 2001; Nakase et al., 2004; Wadia et al., 2004; Fischer et al., 2005; Richard et al., 2005; Murriel and Dowdy, 2006) .”