Dynamic regulation of CXCR1 and CXCR2 homo- and heterodimers.
Although homo- and heterodimerization are reported for some chemokine receptors, it remains unclear whether these functional states are in dynamic equilibrium and how receptor/ligand levels influence oligomerization. In human neutrophils and in cell lines that coexpress the chemokine receptors CXCR1 and CXCR2, we used fluorescence resonance energy transfer techniques to show that these two receptors form homo- and heterodimers. Receptor expression and ligand activation were found to regulate the balance between these complexes, adapting the response to changes in the milieu. CXCL8, a ligand for both receptors, alters heterodimeric complexes, whereas it stabilizes homodimers and promotes receptor internalization. Oligomerization of receptors, together with the regulation of their expression and desensitization, could thus contribute to the fine control of chemokine functions.
Martínez Muñoz
Laura
L
Department of Immunology and Oncology, Centro Nacional de Biotecnología/Consejo Superior de Investigaciones Cientificas, Cantoblanco, Madrid, Spain.
Lucas
Pilar
P
Navarro
Gemma
G
Checa
Ana I
AI
Franco
Rafael
R
Martínez-A
Carlos
C
Rodríguez-Frade
José Miguel
JM
Mellado
Mario
M
D015153:Blotting, Western; D005434:Flow Cytometry; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D016209:Interleukin-8 / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D009504:Neutrophils / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D023062:Receptors, Interleukin-8A / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D023063:Receptors, Interleukin-8B / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D014162:Transfection
D016209:Interleukin-8; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B