11 Signalling Between Cells II Flashcards
Q: What are the 4 different types of receptor? Summarise each. How do they differ in speed of effect delivery?
A: Ionotropic Receptor - ligand binding opens an ion permeable pore
G-protein coupled receptor - ligand binding activates intracellular G-protein
Enzyme linked receptor - ligand binding leads to receptor clustering which activates internal enzymes
Intracellular Receptor - a membrane permeable ligand binds to a receptor inside the cell
intra takes longest as requires transcription
takes longer as you go down
Q: What can a ligand be? (2)
A: neurotransmitter
hormone
Q: Describe the process for ionotropic receptors.
A: signal transduction events
- Ligand binds to the receptor protein
- change in conformation of the channel protein -> opening of a pore
- pore allows ions to move in or out of cell according to their respective concentration gradients
Q: Describe how GABA acts with an ionotropic receptor. Blocked?
A: GABA binds to the receptor (in brain) and causes the opening of the pore which allows an influx of chloride ions
GABA acting on cells will cause a depression of activity (decreased neuronal activity)
If you block the GABA receptor you get hyperexcitability of the CNS and possibly epileptic seizures
Q: What are 2 examples of iotropic receptors?
A: Nicotinic Acetylcholine Receptor is located on skeletal muscle at neuromuscular junctions - it begins the depolarisation which leads to muscle contraction (physiological effect)
-ligand = acetylcholine (ACh)
GABA (A)small
-ligand= gamma-amino butyric acid (GABA)
-location = neuronal (located on many cells in the CNS)
-physiological effect = decreased neuronal activity
Allows transmission of anions
Q: How does a G protein exist?
A: usually heterotrimeric
3 different components (alpha, beta, gamma subunits)
Q: Describe an example of a G protein associated receptor. Process. (8)
A: cardiomyocyte in heart: 7-TM receptor (has 7 transmembrane regions)
- 7-TM receptor and heterotrimeric G protein (associated with GDP) are inactive
- Ligand binds and changes conformation of the receptor (opens up surface of intracellular side of receptor)
- unassociated G-protein binds to the 7-TM receptor
- GDP is exchanged for GTP
- G protein dissociates into 2 active components (GTP provides energy to do this):
- alpha subunit (stays with GTP)
- beta gamma subunit - subunits go and bind to their target proteins
- Once the alpha subunit has attached to the target protein, internal GTPase activity within the subunit causes the GTP molecule to change to a GDP molecule
- alpha subunit unbind from the target protein and reform the heterotrimer with GDP attached -> inactive again
Q: How do you get a G protein associated receptor to remain active?
A: keep ligand bound (will keep activating G protein)
Q: What are the 3 types of G alpha subunits? (isoforms)
A: Gs protein linked receptor
Gi protein linked receptor
Gq protein linked receptor
Q: Describe the Gs protein linked receptor. Example?
A: S = stimulatory
Stimulates adenylate cyclase which converts ATP to cyclic adenosine monophosphate (cAMP)
cAMP increases levels of PKA (protein kinase A)
EXAMPLE: b1-adrenergic receptor
EFFECT: increases heartrate
NOTE: beta blockers act on the b1-adrenergic receptor
Q: Describe the Gi protein linked receptor. Example?
A: I = inhibitory (known as having vagal tone)
Opposite effect to the Gs protein
Inhibits adenylate cyclase thus reducing levels of cAMP and PKA
EXAMPLE: M2-muscarinic receptor
EFFECT: decreases heart rate
Q: Describe the Gq protein linked receptor. Associated with? Example?
A: Activates phospholipase C (PLC)
PLC converts PIP2 —-> IP3 + DAG
IP3 —> increase in intracellular Ca2+
DAG - activates PKC
associated with blood vessels
EXAMPLE: AT-1 angiotensin receptor
EFFECT: vasoconstriction
Q: Describe the process of enzyme-linked signal transduction. When is the signal terminated?
A: 1. Ligand binds and the receptors cluster
- Receptor clustering activates enzymes in the cytoplasmic domain
- Enzymes (that are already attached) phosphorylate receptor
- leads to binding of signalling proteins to the cytoplasmic domain
- Signalling proteins recruit other signalling proteins and a signal is generated within the cell
The signal is terminated when a phosphatase removes the phosphate group
Q: What is the key concept when it comes to the process of enzyme-linked signal transduction?
A: they are clustered together once the ligand binds and that’s how they become activated
can’t be activated by themselves
Q: The vast majority of enzyme linked receptors are linked to? Function?
A: TYROSINE KINASE ENZYMES
Tyrosine kinase phosphorylates any protein which has a tyrosine amino acid within it (a large proportion of the proteins within the cell)
