Chemokine Receptor Dimerization and Chemotaxis

A broad array of biological responses ranging from cell polarization, movement, immune and inflammatory responses, as well as prevention of HIV-1 infection, are triggered by the chemokines, a family of structurally related chemoattractant proteins that bind to specific seven-transmembrane receptors linked to G proteins. Although it was initially believed that chemokine receptors act as monomeric entities, it has now been shown that they function as oligomers. Chemokine receptor homo– and heterodimers are found on the cell membrane; binding to their ligands stabilizes specific receptor conformations and activates distinct signaling cascades. Thorough analysis of the conformations adopted by the receptors at the membrane is therefore a prerequisite for understanding the function of these inflammatory mediators. For study of the chemokine receptor conformations at the cell surface, we focus here on conventional biochemical and genetic methods, as well as on new imaging techniques such as those based on resonance energy transfer; we also evaluate in vitro and in vivo methods to determine certain chemokine receptor functions.