title: Molecular interplays involved in the cellular uptake of octaarginine on cell surfaces and the importance of syndecan-4 cytoplasmic V domain for the activation of protein kinase Cα.
abstract: Arginine-rich cell-penetrating peptides (CPPs) are promising carriers for the intracellular delivery of various bioactive molecules. However, many ambiguities remain about the molecular interplays on cell surfaces that ultimately lead to endocytic uptake of CPPs. By treatment of cells with octaarginine (R8), enhanced clustering of syndecan-4 on plasma membranes and binding of protein kinase Cα (PKCα) to the cytoplasmic domain of syndecan-4 were observed; these events potentially lead to the macropinocytic uptake of R8. The cytoplasmic V domain of syndecan-4 made a significant contribution to the cellular uptake of R8, whereas the cytoplasmic C1 and C2 domains were not involved in the process.
authors.affiliation: Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan; Nanoscience and Nanotechnology Research Center, Research Organization for the 21st Century, Osaka Prefecture University, Naka-ku, Sakai, Osaka 599-8570, Japan. Electronic address: i-nakase@21c.osakafu-u.ac.jp.
authors.forename: Ikuhiko
authors.initials: I
authors.lastname: Nakase
authors.affiliation: Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan.
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Osaki
authors.affiliation: Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan.
authors.forename: Gen
authors.initials: G
authors.lastname: Tanaka
authors.affiliation: Department of Dermatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, Nagasaki 852-8501, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Utani
authors.affiliation: Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan. Electronic address: futaki@scl.kyoto-u.ac.jp.
authors.forename: Shiroh
authors.initials: S
authors.lastname: Futaki
mesh_terms: D002462:Cell Membrane / Q000378:metabolism*; D057846:Cell-Penetrating Peptides / Q000032:analysis / Q000378:metabolism*; D004705:Endocytosis; D004789:Enzyme Activation; D006367:HeLa Cells; D006801:Humans; D009842:Oligopeptides / Q000032:analysis / Q000378:metabolism*; D010873:Pinocytosis; D011485:Protein Binding; D051571:Protein Kinase C-alpha / Q000032:analysis / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D053671:Syndecan-4 / Q000032:analysis / Q000378:metabolism*
chemical_list: D057846:Cell-Penetrating Peptides; D009842:Oligopeptides; D053671:Syndecan-4; C448619:octaarginine; D051571:Protein Kinase C-alpha
keywords: Cell-penetrating peptides; Macropinocytosis; PKCα; Syndecan-4