Receptors and Cell signalling

Question 1

3 ways cells signal to each other?

Answer 1

1. Endocirne
2. Paracrine
3. Autocrine

Question 2

Endocrine

Answer 2

• Synthesised & secreted by signalling cells (e.g. endocrine glands)
• Transported via circulatory system
• Affect distant target cells expressing the receptor

Question 3

Paracrine

Answer 3

• Signalling molecules secreted by a cell
• only affects nearby target cells expressing the receptor

Question 4

Autocrine

Answer 4

Cells respond to signals they secrete themselves
e.g., tumour cells may overproduce and respond to growth factors

Question 5

What are the stages of signal transduction?

Answer 5

1. Release of a primary message as a response to a stimulus
2. Reception of message by a receptor
3. Relay of the detection of the primary message to the cell interior by the generation of an intracellular second message
4. Activation of effector molecules by the second messenger that result in a physiological response
5. Termination of the signal cascade

Question 6

What are the key features of signal transduction?

Answer 6

1. Specificity
2. Amplification by “enzyme cascades”
3. Desensitisation/Adaptation
4. Integration
5. Phosphorylation

Question 7

Specificity

Answer 7

• Molecular complementarity between signal and receptor
• Recpetors for a given signal only present on certain cells

Question 8

Amplification by “enzyme cascades”

Answer 8

Activation of an enzyme associated with a receptor

• Catalyses the activation of many molecules of a second enzyme
• Each of these activates many molecules of a third enzyme etc.
• Results in rapid amplification of signal

Question 9

Desensitisation / Adaptation

Answer 9

• Continuous presence of a signal results in desensitisation - Shuts off receptor or removes it from cell surface
• System can become re-sensitised when stimulus declines

Question 10

Integration

Answer 10

• Multiple signals integrated to produce a unified response
• Cross talk

Question 11

Phosphorylation

Answer 11

Often the end result of a signalling pathway is the phosphorylation of a few specific target proteins
○ Phosphorylation switches the proteins on or off

Protein phosphorylation is carried out by kinases
○ Transfer terminal phosphate of ATP to hydroxyl group on target protein
Dephosphorylation is carried out by phosphatases
○ Catalyse removal of the phosphate by hydrolysis

Question 12

4 Main Receptor Classes (Superfamilies)?

Answer 12

1. Gated ion channels
2. G protein coupled receptors
3. Receptor kinases
4. Nuclear receptors

Question 13

Ligand gated ion channels 3 important properties:

Answer 13

1. Activated in response to specific ligands
2. Conduct ions throughx the otherwise impermeable cell membrane
3. They select among different ions
   When the ligand binds to its site on the receptor, conformational changes cause the channel to open and ions flow through

Question 14

example of a ligand gated ion channel

Answer 14

Nicotinic Acetylcholine Receptor (nAChR)
* Nicotine binds and activates the receptor (agonist)
* Allows Na+ and Ca2+ into the cell
* CNS stimulant - causes enhanced neurotransmitter release
* Also causes release of adrenaline from adrenal gland
○ Fight or flight response

Question 15

Structure of the nACh Receptor

Answer 15

• 5 receptor subunits (polypeptides) form a cluster surrounding a central transmembrane pore
• Two acetylcholine binding sites in the extracellular portion of the receptor
  When acetylcholine molecules bind to both, the channel opens

Question 16

What does each receptor subunit contain

Answer 16

Each subunit has:
○ M1, M2 - always faces towards central pore, M3, M4
○ Total of 20 membrane-spanning helices

Question 17

What does the pore of a receptor consist of?

Answer 17

• M2 of each of the 5 subunits form pore lining
• Have no charged residues (hydrophobic) - no repulsive forces

Question 18

What are the steps in neronal signalling?

Answer 18

When ACh binds to AChR, it initiates a series of events that lead to the transmission of signals between neurons.

1. ACh binding
2. Ion channel activation
3. Ion movement
4. Depolarization
5. Action potential propagation
6. Signal transmission

Question 19

ACh binding

Answer 19

• Acetylcholine is released from the presynaptic neuron into the synapse.
• Binds to the AChR located on the postsynaptic membrane of the target neuron.

Question 20

Ion channel activation

Answer 20

• The binding triggers a conformational change in the receptor protein.
• This opens an ion channel within the AChR complex.

Question 21

Ion movement

Answer 21

There is a flow of positively charged ions across the cell membrane.
Primary ion involved is sodium (Na+).
Sodium ions move from the extracellular fluid into the intracellular space of the neuron.

Question 22

Depolarization

Answer 22

• The influx of sodium ions leads depolarization as the membrane potential becomes less negative.
  negative -> positive
• This depolarization spreads along the neuron’s membrane in the form of an action potential.

Question 23

Action potential propagation

Answer 23

• Depolarization triggers the opening of voltage-gated ion channels,
• Calcium ions (Ca2+) rapidly enter the presynaptic terminal
• Action potential to propagates down the neuron.
• This enables the transmission of the signal from the initial neuron to the next neuron in the network.

Question 24

Signal transmission

Answer 24

• Influx of calcium ions triggers the fusion of synaptic vesicles with the presynaptic membrane.
• This fusion allows the release of neurotransmitters into the synaptic cleft.
• The released ACh diffuses across the synaptic cleft and binds to AChRs on the postsynaptic membrane of the next neuron.
• This initiates the signal transmission process in the receiving neuron, leading to further depolarization and propagation of the signal.