All Flashcards
If a signalling molecule is hydrophilic, where would its receptor be located, and why? Give an example of a hydrophobic signalling molecule.
Located extracellularly, on the surface of the cell because the signal molecule cannot penetrate the lipid bilayer (this is hydrophobic) - so it’s located on the surface.
Hydrophobic molecule - T3/T4, cortisol
Summarise paracrine, endocrine and neurotransmitter communication between cells.
Paracrine- signalling cell releases ligand which binds to local cells and exerts a response.
Endocrine- ligand released from a gland (usually) that enters the blood stream and exerts its action at a tissue distant from the release site.
Neurotransmitter- released from nerve axons as a response to an action potential.
Describe how ligand gated ion channels work. Give an example of such a receptor.
Ligand binds, which causes a pore to open in the centre of the receptor. This allows ions, such as K+ Na+ Ca2+ Cl- to pass through.
nAchR, GABA, Glutamate receptor - all have intrinsic ion channels.
Briefly describe how receptors with integral enzyme activity work
Binding of ligand causes auto phosphorylation of tyrosine residues in the cytoplasmic domain, via protein kinase.
These phosphorylated domains are then recognised either indirectly by signal transducing proteins or directly, by enzymes.
On association, these enzymes are allosterically activated and hence the signal has been transduced to the effector (enzyme).
Explain the basis of 7TMDR
Coupled to GPCRs
GTP replaces GDP
Alpha subunit loses affinity for beta/gamma subunit so they dissociate.
The two dissociated subunits can go and exert their own effects independently.
Hence the signal has been passed on.
Discuss intracellular receptors and how they are stabilised and what effect a ligand has. Name a ligand that uses this method.
They are located either in the cytoplasm or in the nucleus.
In resting state, they are stabilised by HSP or chaperones. On ligand binding, they dissociate from chaperone or HSP and translocate to the nucleus.
Here the affect gene expression and therefore they take a longer time to exert their affect, as transcription and translation is affected.
If a cell is in need of cholesterol, which receptors are synthesised, what is the ligand that will bind, and where are they located (assume the person is healthy and no medical diseases)
It will synthesise apoB receptors, and the ligand is apoB (which is attached to the LDL vesicles).
They are expressed in the coated pits of the cell membrane (accounts for 2% of membrane).
Give 2 ways in which hypercholesterolaemia occurs
Normal apoB receptor but no internalisation
No apoB receptor but internalisation is normal.
Describe the sequence of cholesterol uptake via RME.
Cells requiring cholesterol display apoB receptors in the coated pits.
These invaginate into the cell and bud off into coated vesicles.
Vesicles are rapidly uncoated (clathrin coat)
Uncoated vesicle fuses with an endosome. Ligand is still attached to receptor. pH in endosome is roughly 5-6.
Optimum pH for dissociation of receptor and ligand.
Receptor sequestered to certain domain of endosome where it’s recycled to the cell membrane.
Endosome fuses with lysosome, which hydrolyse the cholesterol esters, releasing cholesterol.
In the context of RME, what does CURL stand for and which organelle does this pertain to ?
Compartment for Uncoupling of Receptor-Ligand.
Endosome.
What is the fate of the receptor and ligand in RME of cholesterol?
Receptor - recycled.
Ligand - degraded.
Briefly explain how Fe3+ is internalised. You should mention the number of Fe3+ that bind to apotransferrin.
2x Fe3+ bind to apotransferrin - forms Transferrin.
Transferrin binds to its receptor which is internalised, same way as LDL.
Vesicle reaches endosome of pH 5-6 and Fe3+ dissociates but the receptor and apotransferrin are still bound.
In the CURL, pH is 7.4 and the two dissociate.
Both ligand and receptor are recycled.
What is the fate of the receptor and ligand in Fe3+ internalisation
Both recycled.
How does RME control the number of insulin receptors expressed, and so the cells sensitivity to circulating insulin.
Insulin receptors are only congregated over coated pits when insulin is bound.
The receptor and bound insulin is internalised. This is then targeted to the lysosome, for degradation.
The degradation reduces the number of receptors and hence sensitivity.
What is the fate of the receptor and ligand in insulin RME.
Both are degraded.
