Dissociation of the G protein βγ from the Gq–PLCβ complex partially attenuates PIP2 hydrolysis

Kankanamge, Dinesh and Ubeysinghe, Sithurandi and Tennakoon, Mithila and Pantula, Priyanka Devi and Mitra, Kishalay and Giri, Lopamudra and Karunarathne, Ajith (2021) Dissociation of the G protein βγ from the Gq–PLCβ complex partially attenuates PIP2 hydrolysis. Journal of Biological Chemistry, 296. p. 100702. ISSN 00219258

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Phospholipase C β (PLCβ), which is activated by the Gq family of heterotrimeric G proteins, hydrolyzes the inner membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2), generating diacylglycerol and inositol 1,4,5-triphosphate (IP3). Because Gq and PLCβ regulate many crucial cellular processes and have been identified as major disease drivers, activation and termination of PLCβ signaling by the Gaq subunit have been extensively studied. Gq-coupled receptor activation induces intense and transient PIP2 hydrolysis, which subsequently recovers to a low-intensity steady-state equilibrium. However, the molecular underpinnings of this equilibrium remain unclear. Here, we explored the influence of signaling crosstalk between Gq and Gi/o pathways on PIP2 metabolism in living cells using single-cell and optogenetic approaches to spatially and temporally constrain signaling. Our data suggest that the Gβγ complex is a component of the highly efficient lipase GaqGTP-PLCβ-Gβγ. We found that over time, Gβγ dissociates from this lipase complex, leaving the less-efficient GaqGTP-PLCβ lipase complex and allowing the significant partial recovery of PIP2 levels. Our findings also indicate that the subtype of the Gγ subunit in Gβγ fine-tunes the lipase activity of Gq-PLCβ, in which cells expressing Gγ with higher plasma membrane interaction show lower PIP2 recovery. Given that Gγ shows cell- and tissue-specific subtype expression, our findings suggest the existence of tissue-specific distinct Gq- PLCβ signaling paradigms. Furthermore, these results also outline a molecular process that likely safeguards cells from excessive Gq signaling.

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IITH Creators:
IITH CreatorsORCiD
Giri, Lopamudrahttp://orcid.org/0000-0002-2352-7919
Mitra, Kishalayhttp://orcid.org/0000-0001-5660-6878
Item Type: Article
Uncontrolled Keywords: Cellular process; Coupled receptors; Heterotrimeric G proteins; Inositol 1 ,4 ,5-triphosphate; Membrane interactions; Molecular process; Partial recovery; Phosphatidylinositol 4 ,5-Bisphosphate;Cell membranes; Chemical activation; Cytology; Hydrolysis; Lipids; Molecular biology; Proteins; Signaling; Tissue
Subjects: Chemical Engineering
Divisions: Department of Chemical Engineering
Depositing User: . LibTrainee 2021
Date Deposited: 28 Jun 2021 09:19
Last Modified: 07 Mar 2022 09:45
URI: http://raiith.iith.ac.in/id/eprint/8028
Publisher URL: http://doi.org/10.1016/j.jbc.2021.100702
OA policy: https://v2.sherpa.ac.uk/id/publication/10347
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