Receptors and membrane turnover Flashcards
Define the term receptor
Receptor – A molecule that recognises specifically a second molecule (ligand), or family of molecules and in response to binding brings about the regulation of a cellular process.
Receptors are classified primarily by their specificity to a physiological signalling molecule. They are then often divided further on the basis of their affinity to a series of antagonists
Note – By definition, receptors have to be silent at rest. If a molecule operates in the absence of it’s ligand, it is not a receptor. Rather it is an Acceptor.
Define the term ligand
Ligand – Any molecule that binds specifically to a receptor site. If the binding of the ligand produces the activation of a receptor, it is an agonist. If a receptor binds without causing activation, blocking the receptor, it is an antagonist.
Why is signal transduction necessary for some signalling molecules?
small hydrophobic molecules may pass through the cell membrane and have direct effects within the cell. However, hydrophobic molecules are unable to do this and so must exert their effect via a membrane protein. This may be in the form of an ion channel, integral enzyme activity (e.g. tyrosine kinase) or coupling through transducing proteins (GPCR)
Discuss intracellular receptors
- acted on by hydrophobic ligands, e.g. steroid hormones
- receptors are bound to chaperones or heat shock proteins at rest
- binding causes dissociation and translocation to the nucleus where it binds to control regions and alters gene expression.
- effects slower than surface ligands as they are dependent on transcription and translation
Explain amplification in cellular signalling
The concentration of many extracellular signalling molecules is very low however their effects may be large. For example, by stimulating the activity of an enzyme, the binding of a chemical signal molecule to a single receptor can cause the modification of hundreds or thousands of substrate molecules. An enzymatic cascade can produce further amplification.
Give an example how responses to different receptors can lead to cellular activation or inhibition
Noradrenaline -1-Adrenoceptors- Increased Heart Rate
Acetylcholine -M2-Muscarinic Receptors- Slowing of HR
Describe the process of phagocytosis
In mammals, phagocytosis is found only in specialised cells, i.e. macrophages and neutrophils. In response to the binding of a particle to receptors in the plasma membrane, the cell extends pseudopods that permit further receptor interactions and membrane invagination/particle internalisation via a ‘membrane zippering’ mechanism. Internalised phagosomes fuse with lysosomes to form phagolysosomes in which the particulate material is degraded.
Describe the process of pinocytosis
Pinocytosis is the invagination of the plasma membrane to form a lipid vesicle. This permits the uptake of impermeable extracellular solutes and retrieval of plasma membrane. Pinocytosis can be sub-divided into two forms, fluid-phase and receptor mediated endocytosis.
Describe the uptake of cholesterol as an example of Receptor Mediated Endocytosis
- Cholesterol is carried from the liver to tissues via LDL
- Cells which require cholesterol exhibit LDL receptors
- These receptors are localised in clusters over clathrin coated pits
- When LDL binds, the pit invaginates to form a coated vesicle
- coated vesicle binds to endosome
- endosome has a lower pH than cytoplasm, therefore the LDL and receptor dissociate. Hence also called a compartment for the uncoupling of receptor and ligand (CURL)
- receptors sequestered and buds of in a vesicle from endosome and is implanted again in the membrane
- remaining endosome with LDL fuses with lysosome
- cholesterol is hydrolysed from the esters and released
Describe the mutations of LDL receptors and how this leads to hypercholesterolaemia
Receptor may not function properly, thus cannot bind to LDLs in the circulation. Alternatively, they may be working but not clustered together in a clathrin coated pit. Finally, they may not be expressed in the membrane properly. This can lead to high circulating levels of cholesterol as it is not being sequestered as normal.
Describe the uptake of iron
- Fe binds to apotransferrin to form transferrin
- Transferrin then binds to transferring receptors at a neutral pH and is endocytosed in a similar fashion to cholesterol.
Describe how membrane enveloped viruses may exploit endocytic pathways to enter cells
Membrane-enveloped viruses and some toxins exploit endocytic pathways to enter cells after adventitious binding to receptors in the plasma membrane.
Once in the endosome, the acidic pH allows the viral membrane to fuse with the endosomal membrane, releasing the viral RNA into the cell where it can be translated and replicated by the host cell’s machinery to form new viral particles.
