title: CXCR4 stimulates macropinocytosis: implications for cellular uptake of arginine-rich cell-penetrating peptides and HIV.
abstract: CXCR4 is a coreceptor of HIV-1 infection in host cells. Through a photocrosslinking study to identify receptors involved in internalization of oligoarginine cell-penetrating peptides (CPPs), we found that CXCR4 serves as a receptor that stimulates macropinocytic uptake of the arginine 12-mer peptide (R12) but not of the 8-mer. We also found that stimulating CXCR4 with its intrinsic ligands, stromal cell-derived factor 1α and HIV-1 envelope glycoprotein 120, induced macropinocytosis. R12 had activity to prevent viral infection for HIV-1(IIIB), a subtype of HIV-1 that uses CXCR4 as a coreceptor for entry into susceptible cells, whereas the addition of a macropinocytosis inhibitor, dimethylamiloride, resulted in enhancement of viral infection. The present study shows that CXCR4 triggers macropinocytosis, which may have implications for the cellular uptake of oligoarginine CPPs and internalization of HIV.
authors.affiliation: Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan.
authors.forename: Gen
authors.initials: G
authors.lastname: Tanaka
authors.forename: Ikuhiko
authors.initials: I
authors.lastname: Nakase
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Fukuda
authors.forename: Ryo
authors.initials: R
authors.lastname: Masuda
authors.forename: Shinya
authors.initials: S
authors.lastname: Oishi
authors.forename: Kazuya
authors.initials: K
authors.lastname: Shimura
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Kawaguchi
authors.forename: Tomoka
authors.initials: T
authors.lastname: Takatani-Nakase
authors.forename: Ulo
authors.initials: U
authors.lastname: Langel
authors.forename: Astrid
authors.initials: A
authors.lastname: Gräslund
authors.forename: Katsuya
authors.initials: K
authors.lastname: Okawa
authors.forename: Masao
authors.initials: M
authors.lastname: Matsuoka
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Fujii
authors.forename: Yasumaru
authors.initials: Y
authors.lastname: Hatanaka
authors.forename: Shiroh
authors.initials: S
authors.lastname: Futaki
mesh_terms: D001120:Arginine; D002462:Cell Membrane / Q000378:metabolism; D057846:Cell-Penetrating Peptides / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D054377:Chemokine CXCL12 / Q000378:metabolism / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000737:chemistry; D015699:HIV Envelope Protein gp120 / Q000378:metabolism / Q000494:pharmacology; D015658:HIV Infections / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism / Q000472:pathogenicity*; D006367:HeLa Cells / Q000187:drug effects / Q000821:virology; D006801:Humans; D010873:Pinocytosis / Q000187:drug effects; D019718:Receptors, CXCR4 / Q000378:metabolism*
chemical_list: D057846:Cell-Penetrating Peptides; D054377:Chemokine CXCL12; D003432:Cross-Linking Reagents; D015699:HIV Envelope Protein gp120; D019718:Receptors, CXCR4; C514793:gp120 protein, Human immunodeficiency virus 1; D001120:Arginine