Research ArticleBiochemistry

FZD5 is a Gαq-coupled receptor that exhibits the functional hallmarks of prototypical GPCRs

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Sci. Signal.  04 Dec 2018:
Vol. 11, Issue 559, eaar5536
DOI: 10.1126/scisignal.aar5536

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FZD5 as a prototypical GPCR

Despite exhibiting sequence and structural similarity to other classes of G protein–coupled receptors (GPCRs), class F family members are generally not considered to be prototypical GPCRs. Wright et al. found that the class F GPCR FZD5 exhibited many of the functional characteristics of GPCRs. FZD5 underwent a conformational change similar to that of conventional GPCRs upon ligand binding. Ligand binding also caused FZD5 to activate signaling through Gαq-containing heterotrimeric G proteins. FZD5-mediated activation of Gαq elicited the production of second messengers, the activation of kinases, and cellular responses typical of G protein activation by classical GPCRs. These findings suggest that FZD5 and other class F GPCRs may not differ from prototypical GPCRs as much as was previously thought.