![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 15, Issue 5, 2492-2508, May 2004
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
||
* The Cancer Research UK Beatson Laboratories, The Beatson Institute for Cancer Research, Glasgow, United Kingdom G61 1BD;
The Division of Immunology, Infection, and Inflammation, Glasgow University, Glasgow, United Kingdom G11 6NT;
Department of Chemistry, Glasgow University, Glasgow, United Kingdom G11 6NT; and
Novartis Forschunginstitut, Vienna, A-1235 Austria
Submitted September 2, 2003;
Revised February 10, 2004;
Accepted February 12, 2004
Monitoring Editor: Howard Riezman
The D6 heptahelical membrane protein, expressed by lymphatic endothelial cells, is able to bind with high affinity to multiple proinflammatory CC chemokines. However, this binding does not allow D6 to couple to the signaling pathways activated by typical chemokine receptors such as CC-chemokine receptor-5 (CCR5). Here, we show that D6, like CCR5, can rapidly internalize chemokines. However, D6-internalized chemokines are more effectively retained intracellularly because they more readily dissociate from the receptor during vesicle acidification. These chemokines are then degraded while the receptor recycles to the cell surface. Interestingly, D6-mediated chemokine internalization occurs without bringing about a reduction in cell surface D6 levels. This is possible because unlike CCR5, D6 is predominantly localized in recycling endosomes capable of trafficking to and from the cell surface in the absence of ligand. When chemokine is present, it can enter the cells associated with D6 already destined for internalization. By this mechanism, D6 can target chemokines for degradation without the necessity for cell signaling, and without desensitizing the cell to subsequent chemokine exposure.
Abbreviations used: 7-TM, seven-transmembrane; CCR, CC-chemokine receptor; CCL, CC-chemokine ligand; CMV, cytomegalovirus; DARC, Duffy antigen receptor for chemokines; GFP, green fluorescent protein; h, human; HEK, human embryonic kidney; HA, hemagglutinin; LEC, lymphatic endothelial cell; m, murine; PBS, phosphate buffered saline; PE, phycoerythrin; PFA, paraformaldehyde; S-PE, Streptavidin-PE; TCA, trichloroacetic acid; TRITC, tetramethylrhodamine isothiocyanate.
Online version of this article contains supporting material. Online version is available at www.molbiolcell.org.
|| Corresponding author. E-mail address: r.nibbs{at}beatson.gla.ac.uk.
This article has been cited by other articles:
|
|
 |
|
  T. N. Hartmann, V. Grabovsky, R. Pasvolsky, Z. Shulman, E. C. Buss, A. Spiegel, A. Nagler, T. Lapidot, M. Thelen, and R. Alon A crosstalk between intracellular CXCR7 and CXCR4 involved in rapid CXCL12-triggered integrin activation but not in chemokine-triggered motility of human T lymphocytes and CD34+ cells J. Leukoc. Biol., October 1, 2008; 84(4): 1130 - 1140. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. A. Zabel, S. Nakae, L. Zuniga, J.-Y. Kim, T. Ohyama, C. Alt, J. Pan, H. Suto, D. Soler, S. J. Allen, et al. Mast cell-expressed orphan receptor CCRL2 binds chemerin and is required for optimal induction of IgE-mediated passive cutaneous anaphylaxis J. Exp. Med., September 29, 2008; 205(10): 2207 - 2220. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. S. McKimmie, A. R. Fraser, C. Hansell, L. Gutierrez, S. Philipsen, L. Connell, A. Rot, M. Kurowska-Stolarska, P. Carreno, M. Pruenster, et al. Hemopoietic Cell Expression of the Chemokine Decoy Receptor D6 Is Dynamic and Regulated by GATA1 J. Immunol., September 1, 2008; 181(5): 3353 - 3363. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F.-Y. Wu, Z.-L. Ou, L.-Y. Feng, J.-M. Luo, L.-P. Wang, Z.-Z. Shen, and Z.-M. Shao Chemokine Decoy Receptor D6 Plays a Negative Role in Human Breast Cancer Mol. Cancer Res., August 1, 2008; 6(8): 1276 - 1288. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Bonecchi, E. M. Borroni, A. Anselmo, A. Doni, B. Savino, M. Mirolo, M. Fabbri, V. R. Jala, B. Haribabu, A. Mantovani, et al. Regulation of D6 chemokine scavenging activity by ligand- and Rab11-dependent surface up-regulation Blood, August 1, 2008; 112(3): 493 - 503. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. W. Kin, D. M. Crawford, J. Liu, T. W. Behrens, and J. F. Kearney DNA Microarray Gene Expression Profile of Marginal Zone versus Follicular B Cells and Idiotype Positive Marginal Zone B Cells before and after Immunization with Streptococcus pneumoniae J. Immunol., May 15, 2008; 180(10): 6663 - 6674. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. V. McCulloch, V. Morrow, S. Milasta, I. Comerford, G. Milligan, G. J. Graham, N. W. Isaacs, and R. J. B. Nibbs Multiple Roles for the C-terminal Tail of the Chemokine Scavenger D6 J. Biol. Chem., March 21, 2008; 283(12): 7972 - 7982. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. F. Neel, L. A. Lapierre, J. R. Goldenring, and A. Richmond RhoB plays an essential role in CXCR2 sorting decisions J. Cell Sci., May 1, 2007; 120(9): 1559 - 1571. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Hansell and R. Nibbs Professional and Part-Time Chemokine Decoys in the Resolution of Inflammation Sci. Signal., May 1, 2007; 2007(384): pe18 - pe18. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Martinez de la Torre, C. Buracchi, E. M. Borroni, J. Dupor, R. Bonecchi, M. Nebuloni, F. Pasqualini, A. Doni, E. Lauri, C. Agostinis, et al. Protection against inflammation- and autoantibody-caused fetal loss by the chemokine decoy receptor D6 PNAS, February 13, 2007; 104(7): 2319 - 2324. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Jacquier, M. Prummer, J.-M. Segura, H. Pick, and H. Vogel Visualizing odorant receptor trafficking in living cells down to the single-molecule level PNAS, September 26, 2006; 103(39): 14325 - 14330. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Otero, M. Groettrup, and D. F. Legler Opposite Fate of Endocytosed CCR7 and Its Ligands: Recycling versus Degradation J. Immunol., August 15, 2006; 177(4): 2314 - 2323. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Liu, G. J. Graham, A. Damodaran, T. Hu, S. A. Lira, M. Sasse, C. Canasto-Chibuque, D. N. Cook, and R. M. Ransohoff Cutting Edge: The Silent Chemokine Receptor D6 Is Required for Generating T Cell Responses That Mediate Experimental Autoimmune Encephalomyelitis J. Immunol., July 1, 2006; 177(1): 17 - 21. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Schiavo, D. Baatar, P. Olkhanud, F. E. Indig, N. Restifo, D. Taub, and A. Biragyn Chemokine receptor targeting efficiently directs antigens to MHC class I pathways and elicits antigen-specific CD8+ T-cell responses Blood, June 15, 2006; 107(12): 4597 - 4605. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. D. Neil, M. M. I. Aasa-Chapman, P. R. Clapham, R. J. Nibbs, A. McKnight, and R. A. Weiss The Promiscuous CC Chemokine Receptor D6 Is a Functional Coreceptor for Primary Isolates of Human Immunodeficiency Virus Type 1 (HIV-1) and HIV-2 on Astrocytes J. Virol., August 1, 2005; 79(15): 9618 - 9624. [Abstract] [Full Text] [PDF]
|
|
