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Constitutive association of cell surface CCR5 and CXCR4 in the presence of CD4
Author(s) -
Wang Jinhai,
Alvarez Raymond,
Roderiquez Gregory,
Guan Ennan,
Norcross Michael A.
Publication year - 2004
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.20161
Subject(s) - cxcr4 , chemokine receptor , ccl5 , chemokine , chemokine receptor ccr5 , chemotaxis , cxcl16 , microbiology and biotechnology , angiogenesis , cxcl14 , receptor , biology , cxc chemokine receptors , transfection , cell migration , stromal cell derived factor 1 , cell , cancer research , t cell , cell culture , immunology , biochemistry , genetics , il 2 receptor , immune system
Abstract Chemokine receptors CCR5 and CXCR4 are the major coreceptors of HIV‐1 infection and also play fundamental roles in leukocyte trafficking, metastasis, angiogenesis, and embyogenesis. Here, we show that transfection of CCR5 into CXCR4 and CD4 expressing 3T3 cells enhances the cell surface level of CXCR4. In CCR5 high expressing cells, cell surface level of CXCR4 was incompletely modulated in the presence of the CXCR4 ligand CXCL12/SDF‐1α. CCR5 was resistant to ligand‐dependent modulation with the CCR5 ligand CCL5/RANTES. Confocal laser microscopy revealed that CCR5 was colocalized with CXCR4 on the cell surface. In CD4 expressing CCR5 and CXCR4 double positive NIH 3T3 cells, immunoprecipitation followed by Western blot analysis revealed that CCR5 was associated with CXCR4 and CD4. CXCR4 and CCR5 were not co‐immunoprecipitated in cells expressing CCR5 and CXCR4 but without CD4 expression. Compared to NIH 3T3CD4 cells expressing CXCR4, the entry of an HIV‐1 X4 isolate (HCF) into NIH 3T3CD4 expressing both CXCR4 and CCR5 was reduced. Our data indicate that chemokine receptors interact with each other, which may modulate chemokine–chemokine receptor interactions and HIV‐1 coreceptor functions. Published 2004 Wiley‐Liss, Inc.