Receptors and Cell signalling Flashcards
3 ways cells signal to each other?
- Endocirne
- Paracrine
- Autocrine
Endocrine
- Synthesised & secreted by signalling cells (e.g. endocrine glands)
- Transported via circulatory system
- Affect distant target cells expressing the receptor
Paracrine
- Signalling molecules secreted by a cell
- only affects nearby target cells expressing the receptor
Autocrine
Cells respond to signals they secrete themselves
e.g., tumour cells may overproduce and respond to growth factors
What are the stages of signal transduction?
- Release of a primary message as a response to a stimulus
- Reception of message by a receptor
- Relay of the detection of the primary message to the cell interior by the generation of an intracellular second message
- Activation of effector molecules by the second messenger that result in a physiological response
- Termination of the signal cascade
What are the key features of signal transduction?
- Specificity
- Amplification by “enzyme cascades”
- Desensitisation/Adaptation
- Integration
- Phosphorylation
Specificity
- Molecular complementarity between signal and receptor
- Recpetors for a given signal only present on certain cells
Amplification by “enzyme cascades”
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
Desensitisation / Adaptation
- 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
Integration
- Multiple signals integrated to produce a unified response
- Cross talk
Phosphorylation
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
4 Main Receptor Classes (Superfamilies)?
- Gated ion channels
- G protein coupled receptors
- Receptor kinases
- Nuclear receptors
Ligand gated ion channels 3 important properties:
- Activated in response to specific ligands
- Conduct ions throughx the otherwise impermeable cell membrane
- 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
example of a ligand gated ion channel
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
Structure of the nACh Receptor
- 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
What does each receptor subunit contain
Each subunit has:
○ M1, M2 - always faces towards central pore, M3, M4
○ Total of 20 membrane-spanning helices
What does the pore of a receptor consist of?
- M2 of each of the 5 subunits form pore lining
- Have no charged residues (hydrophobic) - no repulsive forces
What are the steps in neronal signalling?
When ACh binds to AChR, it initiates a series of events that lead to the transmission of signals between neurons.
- ACh binding
- Ion channel activation
- Ion movement
- Depolarization
- Action potential propagation
- Signal transmission
ACh binding
- Acetylcholine is released from the presynaptic neuron into the synapse.
- Binds to the AChR located on the postsynaptic membrane of the target neuron.
Ion channel activation
- The binding triggers a conformational change in the receptor protein.
- This opens an ion channel within the AChR complex.
Ion movement
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.
Depolarization
- 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.
Action potential propagation
- 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.
Signal transmission
- 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.
