Interaction of Arginine-Rich Peptides with Membrane-Associated Proteoglycans Is Crucial for Induction of Actin Organization and Macropinocytosis
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- 作者：Ikuhiko Nakase ; Akiko Tadokoro ; Noriko Kawabata ; Toshihide Takeuchi ; Hironori Katoh ; Kiyo Hiramoto ; Manabu Negishi ; Motoyoshi Nomizu ; Yukio Sugiura ; Shiroh Futaki
- 刊名：Biochemistry
- 出版年：2007
- 出版时间：January 16, 2007
- 年：2007
- 卷：46
- 期：2
- 页码：492 - 501
- 全文大小：1166K
- 年卷期：v.46,no.2(January 16, 2007)
- ISSN：1520-4995
文摘
Arginine-rich peptides, including octaarginine (R8), HIV-1 Tat, and branched-chain arginine-rich peptides, belong to one of the major classes of cell-permeable peptides which deliver various proteinsand macromolecules to cells. The importance of the endocytic pathways has recently been demonstratedin the cellular uptake of these peptides. We have previously shown that macropinocytosis is one of themajor pathways for cellular uptake and that organization of the F-actin accompanies this process. In thisstudy, using proteoglycan-deficient CHO cells, we have demonstrated that the membrane-associatedproteoglycans are indispensable for the induction of the actin organization and the macropinocytic uptakeof the arginine-rich peptides. We have also demonstrated that the cellular uptake of the Tat peptide ishighly dependent on heparan sulfate proteoglycan (HSPG), whereas the R8 peptide uptake is less dependenton HSPG. This suggests that the structure of the peptides may determine the specificity for HSPG, andthat HSPG is not the sole receptor for macropinocytosis. Comparison of the HSPG specificity of thebranched-chain arginine-rich peptides in cellular uptake has suggested that the charge density of the peptidesmay determine the specificity. The activation of the Rac protein and organization of the actin were observedwithin a few minutes after the peptide treatment. These data strongly suggest the possibility that theinteraction of the arginine-rich peptides with the membrane-associated proteoglycans quickly activatesthe intracellular signals and induces actin organization and macropinocytotis.