Flashcards in MR S6 - Receptors & Membrane Turnover Deck (46)
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What is a receptor?
A molecule which specifically binds to another molecule to illicit a change in a cellular process
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State a few roles of receptors
Signalling via:
Hormones
Neurotransmission
Cellular delivery
Ect
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What is a ligand?
Any molecule that binds specifically to a receptor site
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What is an agonist?
A ligand which binds to a receptor and causes activation of that receptor
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What is an antagonist?
A ligand which binds to a receptor and doesn't cause activation of that receptor
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What is signal transduction?
The transmission of a signal inside the cell when a ligand binds to a receptor on the cell surface
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How may a signal be transduced?
-Integral ion channels
-Integral enzyme activity
-Coupling to effectors through transducing proteins
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Why is signal transduction necessary?
To propagate the signal within the cell - hydrophilic ligands cannot pass the cell membrane so signal transduction is required
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Describe membrane transduction by integral ion channels
Agonist binding causes conformational change and the opening of a gated channel
Channel then permits the movement of ions down their concentration gradient
Eg classical nAChr and non classical Ryanodine receptors
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Describe membrane receptors with integral enzyme activity
Agonist binding to the extracellular domain causes conformational change
This activates an enzyme which form a part of the protein structure
Eg PDGF and linked tyrosine kinase
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Describe tyrosine linked receptors
Autophosphorylate upon ligand binding
Residues recognised by transducing proteins or directly by enzymes
Upon association, effector enzymes are activated which transduce the message into an intracellular chemical event
Eg insulin receptor
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Describe membrane bound receptors with transducing proteins
This family of receptors are known as GPCRs
7 transmembrane domain receptors couple to effector molecules via a transducing protein: a GTP binding regulatory protein or G protein
Effectors may be enzymes or ion channels
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What is integrated signalling?
When separate GPCRs act simultaneously to stimulate or inhibit an effector
The two inputs combine to produce a measured effect
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Give examples of GPCRs
Dopamine receptors, mAChR, 5-HT receptors and light, smell and taste receptors
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Describe the specificity of GPCRs in relation to their distribution
Very specific
Several GPCRs can exist for the same agonist
Eg M1-5 ACh receptors - each type are found in different locations.
Useful as drugs can be targeted at one type of GPCR to only affect a local area.
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Give examples of hormones with intracellular receptors
Hydrophobic hormones eg:
Oestrogen
Testosterone
T3 & T4
Cortisol
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Describe binding to intracellular receptors
Hydrophobic ligands pass through the cell membrane
Bind to intracellular receptors (in resting state these are bound to heat shock or chaperone proteins)
Activated receptor dissociates from it's stabilising protein and moves to the nucleus where it binds to control regions in DNA
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What is a disadvantage of intracellular receptors?
They bind to DNA so they change translation and/or transcription therefore they have a slower effect than extracellular receptors
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How does amplification of signalling molecules occur?
Many ways eg
Stimulation of an enzyme can cause the binding of a single molecule to be amplified to hundreds or thousands of molecules
Enzyme cascades can be triggered, causing further amplification
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Why may amplification of cellular signals be necessary?
The concentrations of extracellular signalling molecules can be very low so amplification may be needed to trigger an appropriate response
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In cardiac pacemaker cells, stimulation of which receptors cause increase and decrease of heart rate?
Increase: β1 adrenoreceptors are activated by noradrenaline
Decrease: M2 muscarinic receptors are activated by acetylcholine
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In hepatocytes, how does hormonal stimulation affect glycogen stores?
Insulin binding to receptors stimulates glycogen synthesis
Glucagon binding to receptors stimulates glycogen breakdown
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Describe phagocytosis
A particle binds to a receptor on the cell membrane
The cell extends pseudopods to invaginate the particle with a membrane zippering mechanism
Internalised phagosomes fuse with lysosomes to form phagolysosomes in which the particle is degraded
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What is pinocytosis?
The invagination of the plasma membrane to form a lipid vesicle
Permits uptake of impermeable extracellular solutes and retrieval of plasma membrane
Sub divided into fluid phase and receptor mediated endocytosis (RME)
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Describe receptor mediated endocytosis (RME)
Specific binding of molecules to cell surface receptors permits the selective uptake of substances into the cell
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Describe the uptake of cholesterol as an example of RME
LDL binds to apoprotein B receptor in clathrin pit on target cell surface
Pit invaginates to form coated vesicles
Coated vesicles are actively (aka using ATP) uncoated
They then fuse with endosomes
LDL particle and receptor dissociate
Receptor is recycled and returns to plasma membrane
Endosome fuse with lysosomes
Cholesterol is hydrolysed from the esters and released into the cell
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Describe the structure of an LDL
Core of fatty acids (esterified cholesterol)
Lipid mono layer of phospholipids, cholesterol and apoprotein B
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How is cholesterol only absorbed by cells that require it?
The target cells have apoprotein B receptors located in clathrin coated pits which spontaneously form on the cell membrane
These pits cover ~2% of the cell surface
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Why do the LDL receptors and particles dissociate in the endosome?
The pH is lower within the endosome than in the cytoplasm (5.5-6.0)
This means the receptor and particle have a lower affinity for each other
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