Heterotrimeric G Protein Subunit Gαq Is a Master Switch for Gβγ-Mediated Calcium Mobilization by Gi-Coupled GPCRs
| Autor: | Junken Aoki, Evi Kostenis, Daniela Wenzel, Nicole Merten, Nina Heycke, Maddalena Vescovo, Bernd K. Fleischmann, Ina Maria Albrecht, Katharina Simon, Alexander Pfeifer, Michaela Matthey, Gabriele M. König, Stephanie Hennen, Francois Marie Ngako Kadji, Felix Häberlein, Bernhard Nieswandt, Timo Vögtle, Kouki Kawakami, Julian Brands, Suzune Hiratsuka, Jaspal Garg, Asuka Inoue, Eva Marie Pfeil, Akos Heinemann, Marie Lise Jobin, Yuki Ono, Kerstin Seier, Davide Calebiro, Ulrike Rick |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Ca
2+ signaling FR900359 Gi GPCR GPR17 Gq heterotrimeric G protein phospholipase Cβ PTX real-time BRET-based IP 3 biosensor Calcium Calcium Signaling Cytosol GTP-Binding Protein alpha Subunits GTP-Binding Protein beta Subunits GTP-Binding Protein gamma Subunits HEK293 Cells Heterotrimeric GTP-Binding Proteins Humans Phospholipase C beta Protein Binding Receptors G-Protein-Coupled Signal Transduction G protein Phospholipase 03 medical and health sciences G-Protein-Coupled 0302 clinical medicine Heterotrimeric G protein Receptors Receptor Molecular Biology 030304 developmental biology G protein-coupled receptor 0303 health sciences biology Active site Cell Biology Cell biology Gq alpha subunit biology.protein Heterotrimeric G Protein Subunit 030217 neurology & neurosurgery |
| Popis: | Mechanisms that control mobilization of cytosolic calcium [Ca2+]i are key for regulation of numerous eukaryotic cell functions. One such paradigmatic mechanism involves activation of phospholipase Cβ (PLCβ) enzymes by G protein βγ subunits from activated Gαi-Gβγ heterotrimers. Here, we report identification of a master switch to enable this control for PLCβ enzymes in living cells. We find that the Gαi-Gβγ-PLCβ-Ca2+ signaling module is entirely dependent on the presence of active Gαq. If Gαq is pharmacologically inhibited or genetically ablated, Gβγ can bind to PLCβ but does not elicit Ca2+ signals. Removal of an auto-inhibitory linker that occludes the active site of the enzyme is required and sufficient to empower "stand-alone control" of PLCβ by Gβγ. This dependence of Gi-Gβγ-Ca2+ on Gαq places an entire signaling branch of G-protein-coupled receptors (GPCRs) under hierarchical control of Gq and changes our understanding of how Gi-GPCRs trigger [Ca2+]i via PLCβ enzymes. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|