Fig. 6: mGlu2/4 trans-activation observed in cAMP inhibition experiments.
From: Elucidating the molecular logic of a metabotropic glutamate receptor heterodimer
a Schematic of the BRET-based cAMP inhibition assay. Agonist-activated group II or III mGlu homodimers or heterodimers couple to and activate the heterotrimeric Gi protein leading to inhibition of adenylyl cyclase and decreased cAMP biosynthesis from adenosine triphosphate (ATP). The cAMP sensor using YFP-Epac-RLuc (CAMYEL)47 was used to detect cAMP inhibition. b (top) Schematic showing experiment probing trans-activation from the mGlu4-to-mGlu2 protomer and corresponding cAMP-inhibition measurements showing L-AP4-concentration-response curves in the absence (DMSO vehicle, black circles) or presence of 50 µM PAMs: VU0155041 (orange squares), PHCCC (cyan triangles), BINA (blue inverted triangles). c (top) Schematic showing experiment probing trans-activation from the mGlu2-to-mGlu4 protomer and corresponding cAMP-inhibition measurements showing DCG IV-concentration-response curves in the absence (DMSO vehicle, black circles) or presence of 50 µM PAMs: VU0155041 (orange squares), PHCCC (cyan triangles), BINA (blue inverted triangles). For plots, symbols represent the mean drug-induced BRET, error bars represent ± SEM, and the exact number of ‘n’ independent experiments and technical replicates are reported in Supplementary Table 1. Source data are provided as a Source Data file.
