Degree
Master of Science
Program
Physiology and Pharmacology
Supervisor
Dr. Peter Chidiac
2nd Supervisor
Dr. Brad Urquhart
Co-Supervisor
Abstract
G protein coupled receptors (GPCRs) promote G protein heterotrimer (Gα·GDP/Gbg) activation.GPCRsignalling is limited via G protein GTPase activity and b-arrestin-receptor interactions. G Protein Signalling Modulators (GPSMs) are proteins that may influence receptor signalling through G protein activity. GPSM3 modulates their activity by binding to Gai-GDP, limiting nucleotide exchange and preventing its re-association to Gbg. The impact of GPSM3 on signalling is unknown.We hypothesize that GPSM3 will decrease Gai-dependent signalling while promoting Gbg-dependent signalling in Gi-coupled GPCRs.
GPSM3 significantly inhibited b-arrestin recruitment to α2A-adrenergic and m-opioid receptors via a Gbg-dependent mechanism,with no effect to Gs- and Gq/11-coupled GPCRs. N-terminal truncation and single point mutations in three distinct regions of GPSM3 decreased the inhibitory effect of GPSM3 on b-arrestin recruitment to α2A-adrenergic and m-opioid receptors.
Thus, our data suggest that GPSM3 negatively regulates b-arrestin-Gi-coupled GPCRinteractions, which could serve as a potential therapeutic target for future pharmaceuticals.
Recommended Citation
Surmanski, Aneta A., "Effects of G Protein Signalling Modulator 3 on Cellular Signalling" (2018). Electronic Thesis and Dissertation Repository. 5526.
https://ir.lib.uwo.ca/etd/5526
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