Debbie Hay-3 Flashcards
How are GCPRs regulated?
G-protein coupled receptor kinases phosphorylate serine and threonine residues on intracellular loops and the C-Terminus domain
This allows the binding of beta arrestin to these phosphorylated residues via its own outer serine residues diminishing the receptors ability to activate G-proteins
The receptor can then be internalised where it can either be targeted for protein degradation or dephosphorylated and recycled
Can also be regulated via presence/absence of hormone
How are second messengers regulated?
cAMP is degraded by phosphodiesterases
How might arrestins promote signalling?
Can act as scaffold proteins leading to the activation of mitogen activated protein kinase cascades
How do GCPRs function in vision?
In vertebrates rhodopsin acts as the dim-light receptor
It is an unusual receptor as it does not bind a ligand but rather light induces a conformational change of a covalently bound chromophore from a cis to a trans conformation
This induces a conformational change in the receptor to activate it
This receptor signals a Galpha(t) -transducin- protein which activates cGMP phosphodiesterase which reduces cGMP levels closing cGMP gated ion channels leading to membrane hyperpolarization and neuronal signalling
This process is controlled through levels of light as in low light levels it is fully active but in lower light levels activity is reduced via increasing phosphorylation and eventually arrestin recruitment
How do GCPRs function in smell?
Each olfactory neuron, found in the olfactory epithelium expresses a single type odorant receptor, activation occurs via a specific ligand which results in activation of Galpha(olf) which activates adenylate cyclase to increase cAMP activation a cyclic nucleotide gated channel which is a non specific cation channel causing an influx of cations and generation of an action potential to inform higher brain structures
Each odorant receptor recognises multiple odorants, and each odorant is recognized by multiple receptors different odorants have different combinations of receptors the perception of smell depends on the combination activated
How do GCPRs function in gene expression?
A downstream consequence of Protein kinase A activation, phosphorylation of CREBP stimulates the expression of specific genes
How do GCPRs function in smooth muscle contraction?
Acetylcholine is released by postganglionic parasympathetic neurons to bind to M3 muscarinic receptors resulting in the activation of Galpha(q) causing an increase in intracellular calcium inducing the formation of Ca2+/calmodulin which can then activate myosin light chain kinase resulting in muscle contraction
How do GCPRs function in pigment dispersal/aggregation?
Physiological colour change is caused by by hormonal stimulation of GCPRs leading to activation of either Galpha(i) or Galpha(s) to cause aggregation or dispersal respectively
This occurs as PKA phosphorylates a protein on pigment granules causing them to disperse, this is maintained by a ser/thr phosphatase inactive so this can occur
In the case of Galpha(i) there will be no activation of PKA so the phosphatase is active driving aggregation of the pigment granules
