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bioRxiv · 10.1101/2023.07.24.550373

Signaling specificity and kinetics of the human metabotropic glutamate receptors.

McCullock, T. W.·Cardani, L. P.·Kammermeier, P. J.
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Abstract

Metabotropic glutamate receptors (mGluRs) are obligate dimer G protein coupled receptors that can all function as homodimers. Here, each mGluR homodimer was examined for its G protein coupling profile using a BRET based assay that detects the interaction between a split YFP-tagged G{beta}1{gamma}2 and a Nanoluc tagged free G{beta}{gamma} sensor, MAS-GRK3-ct-NLuc with 14 specific G proteins heterologously expressed, representing each family. Canonically, the group II and III mGluRs (2&3, and 4, 6, 7&8, respectively) are thought to couple to Gi/o exclusively. In addition, the group I mGluRs (1&5) are known to couple to the Gq/11 family, and generally thought to also couple to the PTX-sensitive Gi/o family; some reports have suggested Gs coupling is possible as cAMP elevations have been noted. In this study, coupling was observed with all 8 mGluRs through the Gi/o proteins, and only mGluR1&5 through Gq/11, and perhaps surprisingly, not G14. None activated any Gs protein. Interestingly, coupling was seen with the group I and II, but not the group III mGluRs to G16. Slow but significant coupling to Gz was also seen with the group II receptors.

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McCullock, T. W., Cardani, L. P., Kammermeier, P. J.. 2023-07-26. Signaling specificity and kinetics of the human metabotropic glutamate receptors.. https://doi.org/10.1101/2023.07.24.550373

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