Signal Transduction Flashcards
(33 cards)
List some functions that G proteins are responsible for
Muscle contraction Stimulus-secretion coupling Catabolic/anabolic processes Light Smell Taste
What do G protein-coupled receptors (GPCRs) do? And how? (in general)
Alter the activity of effectors (enzymes or ion channels)
Do this by activating one or more types of guanine nucleotide binding proteins.
Structure of a G-protein
Heterotrimeric (3 distinct subunits stuck together)
3 distinct subunits α, β, γ
α has a guanine nucleotide binding site
Structure of a GPCR?
Single polypeptide chains
7 transmembrane spanning domains
Extracellular N terminal
Intracellular C terminal
What regions of the GPCR are responsible for binding?
2-3 of the transmembrane domains
Or
The N-terminal region
How does interaction of the G protein with the GPCR activate it?
Causes GTP to exchange for GDP on the G protein α subunit.
GDP -> GTP
What happens after the G protein has been activated?
α-GTP and βγ dissociate.
Each interact with effector proteins
What stops the two sub units interacting with the effector proteins? What happens next?
Until the α-GTPase activity hydrolysed GTP back to GDP.
α-GDP and βγ then reform an inactive heterotrimeric complex.
What does Gs stimulate? What kind of pathway is it?
Adenylyl cyclase to produce cAMP
Stimulatory
What do Gi do? Type of pathway?
Inhibits adenylyl cyclase so there is less cAMP
Inhibitory
What do Gq proteins do?
Interact with the membrane bound enzyme PIP2 to generate the 2nd messengers InsP3 and DAG
What does Gt (transducin) do?
Rhodopsin activates it which in turn activates the enzyme that hydrolyses cGMP ➡️ 5’-GMP
What does the pertussis toxin do to GPCRs?
Contains the enzyme ADP-ribosyl transferase which modifies and inactivates Gi-type proteins. This uncouples receptor-effector linkage.
What does the cholera toxin do?
Contains an enzyme which specifically modifies Gs-type proteins, leading to irreversible activation.
What is retinitis pigmentosa caused by?
A loss of function mutation to rhodopsin.
What is nephron epic diabetes insipidus caused by?
Loss of function mutation to V2 vasopressin receptor
What is familial male precocious puberty caused by?
A gain of function mutation (where the receptor is effective without the ligand) to the lute using hormone receptor.
What activates and what inhibits adenylyl cyclase?
Activated via Gs and inhibited by Gi
What does adenylyl cyclase do? What does this lead to?
Hydrolyses ATP to generate cAMP
cAMP interacts with a specific protein kinase (PKA)
PKA then phosphorylates a variety of other proteins within the cell to affect activity.
What effects does adenylyl cyclase have on the cell?
Increased glycogenolysis and gluconeogenesis in the liver
Increased lipolysis in adipose tissue
Relaxation of smooth muscle
Positive inotropic and chronotropic effects in the heart
What is phospholipase C
An enzyme that hydrolyses membrane phospholipid PIP2 ➡️ IP3
What activates phospholipase C?
Gq
What does IP3 do?
Interacts with specific intracellular receptors on the ER to allow Ca2+ to leave the ER lumen and enter the cytoplasm.
What is cyclic GMP phosphodiesterase and what does it do?
A specialised mechanism found in the photoreceptors of the retina.
Rhodopsin is excitated by a photon of light which causes Gt to regulate the breakdown of the second messenger cGMP
Causes channel closure and membrane hyperpolarisation.
