MR S6 - Receptors & Membrane Turnover Flashcards
State a few roles of receptors
Signalling via: Hormones Neurotransmission Cellular delivery Ect
What is a receptor?
A molecule which specifically binds to another molecule to illicit a change in a cellular process
What is a ligand?
Any molecule that binds specifically to a receptor site
What is an agonist?
A ligand which binds to a receptor and causes activation of that receptor
What is an antagonist?
A ligand which binds to a receptor and doesn’t cause activation of that receptor
What is signal transduction?
The transmission of a signal inside the cell when a ligand binds to a receptor on the cell surface
How may a signal be transduced?
- Integral ion channels
- Integral enzyme activity
- Coupling to effectors through transducing proteins
Why is signal transduction necessary?
To propagate the signal within the cell - hydrophilic ligands cannot pass the cell membrane so signal transduction is required
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
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
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
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
What is integrated signalling?
When separate GPCRs act simultaneously to stimulate or inhibit an effector
The two inputs combine to produce a measured effect
Give examples of GPCRs
Dopamine receptors, mAChR, 5-HT receptors and light, smell and taste receptors
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.
Give examples of hormones with intracellular receptors
Hydrophobic hormones eg: Oestrogen Testosterone T3 & T4 Cortisol
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
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