The couple G protein-coupled receptor-G protein: preassembly versus agonist-induced interaction
2014
Ayoub, Mohammed Akli
The investigation of the physical and functional interaction of the G protein-coupled receptors (GPCRs) with their cognate heterotrimeric G proteins constitutes one of the most evolved aspects in this family of cell surface receptors. The development of the energy transfer-based approaches, bioluminescence or fluorescence resonance energy transfer (BRET or FRET, respectively), has strongly contributed to such advance. Using protease-activated receptors 1 and 2 (PAR1 and 2) as model for their multiple G protein coupling profiles, we revealed a preassembly between the two receptors and Gαi1 and Gαo proteins whereas their association with Gα12 occurred only upon receptor activation. Kinetic analysis in real-time and live cells showed important differences in the activation between these two modes of coupling which may be consistent with their implication in the physiological responses of PARs. Together, our finding indicate that preassembly or agonist-promoted association depend on receptor-G protein pair representing the key mechanisms of temporal and spatial regulation and integration of the multiple G protein coupling and signaling of GPCRs.
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