GPCR βγ Spatiotemporal Flashcards
What do GAPs do?
Accelerate hydrolysis of GTP bound to Gα and thus promote Gβγ deactivation
What are the downstream effects of GAPs?
- Inhibit steady-state signaling,
- Accelerate signal termination when receptor agonist is removed
- Alter receptor selectivity among G proteins
- Suppress basal (receptor-independent) signal output
How do Gβγ’s interact with GAPs?
Gβγ subunits have been shown to inhibit the activity of G protein GAPs in solution-phase, single turnover assays (Wang et al.,1997). This may support continued activation of G protein signalling, affecting the time course of response.
How does Gα modulate spatiotemporal aspects of Gβγ signalling?
inhibiting Gβγ interactions with its effectors through Gα-binding site on Gβ
What evidence demonstrated that Gα inhibits Gβγ?
Lyengar and co-workers (1995), who found a peptide from type II adenylate cyclase (ACII) that bound to Gβγ and blocked its activation of various effectors, suggesting that part of the effector binding site is shared between ACII, GIRK, and PLCβ
What experiments localized Gβ binding to Gα-binding region ?
Cross-linking and docking experiments localized the binding site to a part of the Gα-binding region (Lyengar et al., 1997).
What happens when β-ARs are stimulated by agonist?
When β-ARs are stimulated by agonist, the dissociated G protein βγ subunits interact with βARKs via their pleckstrin-homology domains, bringing the kinases within close proximity of the transmembrane β-ARs.
How do βARKs facilitate desensitisation?
Phosphorylation of β-ARs by βARKs leads to the interaction of β-ARs with β-arrestin adaptor proteins which facilitate the internalization of receptors into clathrin-coated pits and endosomic vesicles.
How many isoforms of Gβ and γ?
5 and 12
What type of studies suggest isoform dependence for Gβγ dimerization and specificity (who)?
Variable phenotypes resulting from genetic ablation of individual Gβ and Gγ subunits
Albert et al., 2002
Which βγ isoform mediates CaV inhibition by somatostatin receptors (who)?
β1γ3 (Yim et al.,2017)
What isoform of γsubunit do muscarinic receptors bind to (who)?
somatostatin receptors coupling to CaV’s with Gγ3, but the muscarinic receptor was shown to couple to CaV’s via Gγ4 (Kleuss et al.,1993)
How does βγ vary in the brain (who)?
Gβγ subunits have distinct expression patterns in the brain (Yim et al.,2017)
How do Gβ1γ2 and Gβ1γ1 differ in their mediation of Ca2+ exocytosis (who)?
Gβ1γ2 has a 20-fold higher potency than Gβ1γ1 at inhibiting Ca2+ triggered exocytosis (Blackmer et al.,2005)
