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

Autor: Shahriar M. Khan, Phan Trieu, Mélanie Robitaille, Sarah Gora, Terence E. Hébert, Stephane Angers, Geeda M. Houranieh, Adam Min, Ashley M. Jacobi, Darlaine Pétrin, Rhiannon I. Campden, Mark A. Behlke
Rok vydání: 2015
Předmět:
Transcription
Genetic
G protein
MAP Kinase Signaling System
Biology
Cholinergic Agonists
Transfection
03 medical and health sciences
0302 clinical medicine
GTP-Binding Protein gamma Subunits
Humans
Calcium Signaling
RNA
Messenger
Promoter Regions
Genetic
030304 developmental biology
Calcium signaling
G protein-coupled receptor
Mitogen-Activated Protein Kinase 1
Receptor
Muscarinic M3
0303 health sciences
Binding Sites
Mitogen-Activated Protein Kinase 3
Dose-Response Relationship
Drug
Effector
HEK 293 cells
GTP-Binding Protein beta Subunits
Muscarinic acetylcholine receptor M3
Cell Biology
Receptors
Muscarinic
Hedgehog signaling pathway
Cell biology
G beta-gamma complex
HEK293 Cells
Gene Expression Regulation
Carbachol
RNA Interference
Protein Multimerization
030217 neurology & neurosurgery
Signal Transduction
Zdroj: Cellular signalling. 27(8)
ISSN: 1873-3913
Popis: 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.
Databáze: OpenAIRE
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