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Identification of the tethered peptide agonist of the adhesion G protein-coupled receptor GPR64/ADGRG2

The epididymis-specific adhesion G protein-coupled receptor (aGPCR) GPR64/ADGRG2 has been shown to be a key-player in the male reproductive system. As its disruption leads to infertility, GPR64 has drawn attention as potential target for male fertility control or improvement. Like the majority of aG...

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Published in:Biochemical and biophysical research communications 2015-08, Vol.464 (3), p.743-747
Main Authors: Demberg, Lilian M., Rothemund, Sven, Schöneberg, Torsten, Liebscher, Ines
Format: Article
Language:English
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Summary:The epididymis-specific adhesion G protein-coupled receptor (aGPCR) GPR64/ADGRG2 has been shown to be a key-player in the male reproductive system. As its disruption leads to infertility, GPR64 has drawn attention as potential target for male fertility control or improvement. Like the majority of aGPCRs GPR64 is an orphan receptor regarding its endogenous agonist and signal transduction. In this study we examined the G protein-coupling abilities of GPR64 and showed that it is activated through a tethered agonist sequence, which we have previously identified as the Stachel sequence. Synthetic peptides derived from the Stachel region can activate the receptor, opening for the first time the possibility to externally manipulate the receptor activity. [Display omitted] •Signal transduction and activation mechanism of the orphan GPR64 were investigated.•GPR64 elevates basal cAMP production in transfected cells.•GPR64 is specifically activated through a tethered agonist.•Activated GPR64 shows promiscuous G-protein coupling.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2015.07.020