Using a new quantitative framework for evaluation of receptor dimerization using bioluminescence energy transfer (BRET), Simon Davis and colleagues at the University of Oxford present evidence that the signals arising from BRET measurements, and interpreted as evidence of dimerization, are the result of random interactions and not evidence of stable complexes.
Although researchers have known that random interactions could produce signals indicative of dimerization, this possibility had been discounted. These new results indicate that the case may not be a clear as previously believed. Read the paper here.
There is no doubt that many cell membrane receptors organize themselves as dimers or higher order oligomers. For a long time a subgroup of G protein-coupled receptors, the Class A GPCRs, were considered to be exceptions to this. However, experiments using BRET and other methods provided evidence that these receptors also function as homo- and even hetero-dimers. This conclusion has been widely accepted.
The results by Davis and colleagues are not sufficient to overturn all the evidence in support of GPCR dimerization but the new BRET framework does provide the expected results using control receptors whose dimerization state is unquestioned. This suggests that the dimerization status of some receptors may need to be reassessed.
We encourage readers to post their opinions on this method and its controversial results.
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Everyone has been waiting to find out what Dr. Michel Bouvier thought of the paper by James et al. He and several coauthors have now published their reply here and James et al. have responded.
Add your thoughts regarding the issues raised and help the community figure out how receptor dimerization can be best assessed by BRET.