Receptors and signalling

Question 1

Neurons and neurotransmitters

Answer 1

• Send messages through electrical pulses along their length
• Have gaps between each neurone called synapses which is too big for electrical pulses to pass through
• The communication between nerve cells involves rapid release and diffusion of a neurotransmitter (NT) to antoher cell where it binds to a receptor resulting in a change in the properties of the postsynaptic cell

Question 2

General receptor principles

Answer 2

• All receptors have membrane proteins which have a hydrophobic belt that allows them to sit in the bilayer
• Domains are the chunk of the membrane protein that has a certain shape = intracellular (inside cell), extracellular (outside cell)

Question 3

How do membrane protein receptors work?

Answer 3

1. Chemical messenger (neurotransmitter/hormone=ligand) binds to receptor
2. This induces a change in the protein conformation affecting the region inside the cell
3. The changed conformation activates the intracellular domain
4. After sending the message many times, the chemcial messenger leaves

Question 4

Ion channel receptors

Answer 4

• They can open and close to let ions flow in and out
• Transports along the concentration gradient (high conc outside cell and low conc inside the channel will open to allow the ions to flow into the cell)

Question 5

Ion channel gating

Different stimuli

Answer 5

1. Voltage gated = if the voltage around the channel changes it will open
2. Ligand gated (extracellular) = binding from outside of the cell
3. Ligand gated (intracellular) = binding from inside of the cell

Question 6

G-protein-coupled receptors (GPCRs)

Answer 6

• Activated by neurotransmitters and peptide hormones
• Ligand binding results in activation or deactivation of certain membrane-bound enzymes called G-proteins
• On the extracellular side there is a place for things to bind to a ligand
• On the intracellular side it is more complicated which binds and activates G-proteins
• 7 helical transmembrane domains
  1. Messenger binds to the receptor, this opens the binding site for the G-protein to bind changing the shape of the receptor
  2. When the G-protein binds it is activated

Question 7

G-protein signal transduction

Answer 7

1. Binding of the neurotransmitter changes the shape of the receptor
2. This allows the G-protein hosting GDP in the alpha subunit to bind which changes the conformation of the G-protein, releasing GDP and creates a pocket which GTP binds to
3. Binding of GTP causes another conformational change and this results in the alpha subunit departing separately
4. The alpha subunit then diffuses along the membrane to adenylate cyclase which is then activated to catalyse ATP
5. The alpha subunit has intrinsic GTPase activity, resulting in GTP to become GDP over time
6. This reverses binding and deactivates adenylate cyclase

Question 8

Phosphorylation

Answer 8

1. cAMP activates protein kinase A
2. Protein kinase A phosphorlyates other specific proteins
3. Phosphorylation changes their conformation and activates them in turn
4. Each step can have multiple turnovers = huge signal amplification

Question 9

Kinase receptors

Answer 9

• Binding of the ligand on the extracellular side results in direct activation of the protein as a kinase on the intracellular side
• 1 helical transmembrane domain
  1. Messenger binds to receptor
  2. This changes the active site on the intracellular side which allows for molecules to go from A to B

Question 10

Agonists, antagonists and inverse agonists

Answer 10

• Agonist = a ligand that binds to and provokes a signal from a receptor via conformational changes to produce the active state
• Antagonist = a ligand that binds to a receptor and induces no signal, blocks agonist binding and hinders conformational switch to active state
• Partial agonist = binds and provokes a signal, but diminished compared to a full agonist, binding is suboptimal and conformational switch may not fully engage
• Inverse agonist = removes any base-level activity the receptor has in absence of the ligand