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Albizu L.,French National Center for Scientific Research | Albizu L.,Institute National Of La Ssante Et Of La Recherche Medicale | Albizu L.,Uuniversite Montpellier 1 and 2 | Albizu L.,Mount Sinai School of Medicine | And 35 more authors.
Nature Chemical Biology

G protein-coupled receptor (GPCR) oligomers have been proposed to play critical roles in cell signaling, but confirmation of their existence in a native context remains elusive, as no direct interactions between receptors have been reported. To demonstrate their presence in native tissues, we developed a time-resolved FRET strategy that is based on receptor labeling with selective fluorescent ligands. Specific FRET signals were observed with four different receptors expressed in cell lines, consistent with their dimeric or oligomeric nature in these transfected cells. More notably, the comparison between FRET signals measured with sets of fluorescent agonists and antagonists was consistent with an asymmetric relationship of the two protomers in an activated GPCR dimer. Finally, we applied the strategy to native tissues and succeeded in demonstrating the presence of oxytocin receptor dimers and/or oligomers in mammary gland. 96021130 96021131 © 2010 Nature America, Inc. All rights reserved. Source

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