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Cell Signal. 2015 Aug;27(8):1597-608. doi: 10.1016/j.cellsig.2015.04.007. Epub 2015 Apr 23.

Gβ4γ1 as a modulator of M3 muscarinic receptor signalling and novel roles of Gβ1 subunits in the modulation of cellular signalling.

Author information

1
Department of Pharmacology and Therapeutics, McGill University, Montréal, Québec H3G 1Y6, Canada.
2
Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario M5S 3M2, Canada.
3
Integrated DNA Technologies, Inc., Coralville, IA 52241, United States.
4
Department of Pharmacology and Therapeutics, McGill University, Montréal, Québec H3G 1Y6, Canada. Electronic address: terence.hebert@mcgill.ca.

Abstract

Much is known about the how Gβγ subunits regulate effectors in response to G protein-coupled receptor stimulation. However, there is still a lot we don't know about how specific combinations of Gβ and Gγ are wired into different signalling pathways. Here, using an siRNA screen for different Gβ and Gγ subunits, we examined an endogenous M3 muscarinic receptor signalling pathway in HEK 293 cells. We observed that Gβ(4) subunits were critical for calcium signalling and a downstream surrogate measured as ERK1/2 MAP kinase activity. A number of Gγ subunits could partner with Gβ(4) but the best coupling was seen via Gβ(4)γ(1). Intriguingly, knocking down Gβ(1) actually increased signalling through the M3-mAChR most likely via an increase in Gβ(4) levels. We noted that Gβ(1) occupies the promoter of Gβ(4) and may participate in maturation of its mRNA. This highlights a new role for Gβγ signalling beyond their canonical roles in cellular signalling.

KEYWORDS:

Co-transcriptional regulation; G protein-coupled receptors; G proteins; Gβγ Signalling; RNA interference screen; Signalling specificity

PMID:
25916507
DOI:
10.1016/j.cellsig.2015.04.007
[Indexed for MEDLINE]

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