TY - JOUR
T1 - CXCR4 stimulates macropinocytosis
T2 - Implications for cellular uptake of arginine-rich cell-penetrating peptides and HIV
AU - Tanaka, Gen
AU - Nakase, Ikuhiko
AU - Fukuda, Yasunori
AU - Masuda, Ryo
AU - Oishi, Shinya
AU - Shimura, Kazuya
AU - Kawaguchi, Yoshimasa
AU - Takatani-Nakase, Tomoka
AU - Langel, Ülo
AU - Gräslund, Astrid
AU - Okawa, Katsuya
AU - Matsuoka, Masao
AU - Fujii, Nobutaka
AU - Hatanaka, Yasumaru
AU - Futaki, Shiroh
N1 - Funding Information:
This work was supported in part by Grants-in-Aid for Scientific Research and the Targeted Protein Research Program from the Ministry of Education, Culture, Sports, Science and Technology of Japan. R.M. is grateful for research fellowships from the Japan Society for the Promotion of Science for Young Scientists. This study was also supported by the Swedish Research Council, the Swedish Foundation for Strategic Research, and the Swedish Governmental Agency for Innovation Systems (project no. MDB09-0015) (to Ü.L. and A.G.), and the Strategic Japanese-Swedish Cooperative Program on “Multidisciplinary BIO” from the Japan Science and Technology Agency and VINNOVA (to S.F.).
PY - 2012/11/21
Y1 - 2012/11/21
N2 - 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-1IIIB, 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.
AB - 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-1IIIB, 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84870008010&partnerID=8YFLogxK
U2 - 10.1016/j.chembiol.2012.09.011
DO - 10.1016/j.chembiol.2012.09.011
M3 - Article
C2 - 23177198
AN - SCOPUS:84870008010
SN - 1074-5521
VL - 19
SP - 1437
EP - 1446
JO - Chemistry and Biology
JF - Chemistry and Biology
IS - 11
ER -