CellSig6 - 20 Flashcards
Outline three forms of desensitisation
Receptor inactivation, sequestration, down-regulation
What causes desensitisation?
Prolonged exposure to high concentrations of signal, adaptive/protective response, reversible process
What is the role of cAMP?
Small intracellular mediator
What is the normal IC [cAMP]?
10-7M
What [cAMP] can be reached when EC signal attaches?
Increases by >20 fold
How is cAMP synthesised?
From ATP by PM bound adenylyl cyclase
What is cAMP continually degraded by?
cAMP phosphodiesterase
How does cAMP phosphodiesterase function?
Hydrolyses cAMP to 5’AMP
Outline the regulation of adenylyl cyclase
Gs activates, Gi inhibits
How does cholera toxin affect cAMP function?
Transfers ADP ribose from NAD+ to Gs-a, inhibiting GTP hydrolysis, and causes continuous cAMP production
How does pertussis toxin affect cAMP function?
Transfers ADP ribose from NAD+ to Gi-a, preventing receptor interaction, and halts all cAMP production
How does PKA work?
4 subunits, 2 to bind with cAMP, two catalytic; cAMP binds, catalytic subunits activate
What is PKA’s role in gene transcription?
Activates CREB in nucleus, whichis phosphrylated and binds CREB-binding protein (CBP), leading to activated target gene transcription
How can G-proteins directly regulate ion channels?
Direct binding of b-g to ion channels such as muscarinic acetylcholine receptors
How can G-proteins indirectly regulate ion channels?
Phosphrylation of ion channels by G-protein regulated kinases such as PKA/PKC; OR cyclic-nucleotide gating of ion channels
What is Golf involved in?
Olfactory sensation
How is Golf involved in olfactory sensation?
Activated by GPCR, activates adenylyl cyclase, cAMP produced opens Na channels, allowing depolarisation of neuron
Outline G-protein involvement in response to light
1 photon + 11-cis trans > all-trans > activates rhodopsin (GPCR) > G-transducin (Gt) release > closing of cGMP-gated Na channels
Outline amplification of the G-transducin pathway
1 photon > 1 rhodopsin > 500 Gt > 500 cGMP activation > 10^5 cGMP hydrolysed > 250 channels close > 10^7 cations prevented from entry > membrane-pot altered by 1mV
How is rhodopsin desensitised?
Phosphorylated by GPCR kinase (GRK), then bound by arrestin, uncoupling it
