MnR S6 - Receptors and receptor mediated endocytosis Flashcards
List the groups of secreted chemical signalling molecules according to their function
Local chemical mediators, hormones, neurotransmitter
Define receptor
Molecule that recognises specifically a second molecule (ligand) or family of molecules and which in response to a ligand binding brings about regulation of a cellular process
List some roles of ligands in cellular physiology
- Signalling by hormones
- Neurotransmission
- Cellular delivery
- Control gene expression
- Cell adhesion
- Modulation of immune response
- Sorting intracellular proteins
- Release of intracellular calcium ion stores
Define ligand
Any molecule that binds specifically to a receptor site. May be an agonist or antagonist
How does the binding affinity for ligands at receptors compare to substrates and allosteric regulators at enzyme sites?
Binding affinity much higher between ligands and receptors (KD) than KM
Outline another key difference between ligand and receptor binding and enzyme and substrate binding
Substrate molecule is chemically modified by a chemical reaction catalysed by the active site whereas ligand bound to a receptor site is not altered
How do acceptors differ from receptors?
Operate normally in the absence of ligand and ligand binding alone produces no response
List the four methods of signal transduction
- Membrane-bound receptor with integral ion channel
- Membrane-bound receptor with integral enzyme activity
- Membrane-bound receptor which couples to effectors via transducing proteins
- Intracellular receptors
How can receptors be classified?
- According to the specific physiological signalling molecule recognised
- Sub-classified by affinity of antagonists
Describe the structure of the nAChR and the ions it allows in
- Five sub-unit made up of 4 transmembranous domains each
- K+, Na+ and Ca2+
How does the structure of the nAChR ensure that only cations move through?
Contains charge residues
Give example of other membrane-bound receptors with integral ion channels
- GABA receptor
- Glycine receptor
- Glutamate receptor
Which enzyme are growth factor receptors: EDF, PDGF and insulin linked to?
Tyrosine kinase
How do tyrosine kinase linked receptors work?
- Ligand binds stimulating auto-phosphorylation of the cytoplasmic side of the receptor
- An enzyme OR a transducer then recognises the phosphotyrosine which activates the phosphorylation pathway
What is another name for membrane-bound receptors which couple to effectors via transducing proteins?
7TMD receptors which are coupled through G-proteins enzymes of channels
Where is the binding domain located on 7TMD receptors?
Normally within the plane of the bilayer or sometimes at N-terminus
Where is the G-protein coupling domain located?
Cytoplasmic side of membrane near the C-terminus
Outline how adrenaline binding to beta-adrenoceptors is transduced into the cell
- Adrenaline binds
- GDP bound to third sub-unit (alpha) is released
- GTP binds to the alpha sub-unit
- The three sub-units dissociate
- Alpha subunit goes on to activate adenylyl cyclase
How are intracellular receptors kept silent at rest?
Inhibitory protein complex blocks DNA binding domain and is released when steroid hormone binds
What is phagocytosis and by what mechanism does it occur?
Internalisation of particulate by the zippering mechanism
What is pinocytosis and what is its function?
Invagination of the plasma membrane to form a vesicle, enabling the uptake of extracellular solutes
What is endocytosis?
Selective internalisation of molecules into the cell by binding of specific cell surface receptors
What is the clathrin coat and how it is formed?
Coated pits form spontaneously from clathrin triskelions, made up of hexagons and pentagons forming three light and three heavy chains
How is the clathrin coat removed?
Vesicles are uncoated in an ATP-dependent reaction
List two coat proteins other than clathrin and where they would be found
- COP I - endoplasmic reticulum
- COP II - golgi
By which two mechanisms can mutations in LDL receptors result in hypercholesterolemia?
Non functional receptor - No LDL binding, normal coated pits and internalisation
Receptor binding normal - no internalisation, LDL receptors widely distributed on cell surface, deletion of c-terminal cytoplasmic domain prevents interaction with clathrin coat
What causes the dissociation between LDL receptors and LDL?
Low pH in the endosome/compartment of uncoupling receptor and ligand (CURL) caused by the H+-ATPase which pumps protons into the endosome
What is the fate of the ligand and receptor in LDL uptake?
Ligand - degraded
Receptor - recycled
Outline process of Fe3+ uptake by transferrin
- Ferrotransferrin bind to transferrin receptors
- Uptake into cell
- pH in vesicle decreased due to H+-ATPase
- Fe3+ released into cytosol
- Apotransferrin and receptor are recycled to the cell surface
- Neutral pH of surface compared to the endosome causes dissociation of receptor
- Both receptor and ligand recycled
In insulin uptake, what is the fate of the ligand and receptor?
Ligand and receptor are both degraded
What is the fate of the ligand and receptor in immunoglobulin uptake?
Both transported
How does entry of membrane-enveloped virus into cells take advantage of receptor mediated endocytosis?
- By binding to cells by fortuitous association with cell receptors
- Enters cells via clathrin-coated pits
- By unfolding hydrophobic domains in membrane fusion proteins due to the acidic pH of the endosome
- By inserting membrane fusion proteins into the endosome membrane causing membrane fusion and release of genomic RNA into cell cytoplasm
What do cholera and diphtheria toxins bind to?
GM1 ganglioside
