BABS2202 Chap.5 Cell Signalling and GPCR Logic
Cell Signalling and GPCR Logic
Cell signalling converts information outside or inside a cell into a change in behaviour. The core vocabulary is functional: ligand, receptor, transducer, effector, second messenger, target and response. Specificity depends on which receptors and downstream components a cell expresses, where they are located and how the network is wired.
Sensitivity, amplification, duration, feedback and adaptation determine more than the presence of a pathway name. A transient signal and a sustained signal can produce different outcomes even when they pass through some of the same proteins.
G-protein-coupled receptors provide a clean model. Ligand binding changes receptor conformation, promoting exchange of nucleotide on a heterotrimeric G protein.
Activated subunits regulate effectors that produce or alter second messengers, which then influence kinases, channels or other targets. Signal termination is active: ligand dissociation, nucleotide hydrolysis, receptor phosphorylation, arrestin engagement, internalisation, messenger removal and protein dephosphorylation can each limit output. Experimental diagnosis therefore follows the signal in order.
If ligand binds and the G protein activates but the second messenger does not accumulate, the candidate defect moves downstream; a single endpoint still cannot distinguish failed production from rapid degradation.
What this chapter covers
- 01
Local, synaptic, endocrine and contact-dependent signalling as different delivery arrangements
- 02
Receptor expression and cellular competence as foundations of response specificity
- 03
Heterotrimeric G-protein activation, nucleotide exchange, subunit effectors and intrinsic shutoff
- 04
Second messengers as distributed, amplified and spatially regulated signals
- 05
Kinase and phosphatase balance in reversible target-state changes
- 06
Feedback, feed-forward control, adaptation, receptor desensitisation and internalisation
- 07
Pathway diagnosis using ordered readouts, time courses, agonists, antagonists and rescue
Locating a low-second-messenger phenotype
- +1Normal upstream events locate the unresolved defect at messenger production, removal or a closely connected step.
- +1A disabled effector enzyme predicts low production even when messenger degradation is restrained.
- +1Excessive removal may produce a brief early pulse and should respond to selective inhibition of the degrading activity.
- +1Use a rapid time course plus degradation inhibition and a receptor-independent effector activator with matched controls.
Key terms
- Ligand
- A molecule whose binding changes the state of a receptor or other target; binding affinity alone does not specify the downstream response.
- GPCR
- A seven-transmembrane receptor that changes conformation after ligand binding and can regulate heterotrimeric G proteins.
- Heterotrimeric G protein
- A membrane-associated alpha, beta and gamma complex that cycles between nucleotide states to couple activated receptors to effectors.
- Second messenger
- An intracellular molecule or ion whose regulated concentration or availability helps carry information beyond the receptor.
- Desensitisation
- Reduction in responsiveness during continued or repeated stimulation through receptor, transducer or downstream regulatory changes.
- Dose–response relationship
- The measured response across input concentrations, shaped by receptor occupancy, coupling, amplification, feedback and assay limits.
Cell Signalling and GPCR Logic FAQ
Does receptor binding prove pathway activation?
No. Binding establishes recognition under the assay conditions. The receptor may fail to adopt an active conformation, couple to its G protein or reach the correct membrane compartment. Measure a receptor-proximal activation event and a downstream response separately.
Why can the same ligand cause different responses in different cells?
Cells differ in receptor abundance, G-protein and effector expression, scaffold proteins, second-messenger handling, transcriptional state and feedback. The same input can therefore enter different networks or reach different thresholds. Name the cell context when predicting an outcome.
Is a larger second-messenger signal always a stronger biological response?
Not necessarily. Targets can saturate, inhibitory feedback can increase, spatially restricted messenger pools can matter more than the whole-cell average, and response identity can depend on duration rather than peak. Measure the final relevant phenotype as well as the messenger.
How does a GPCR signal stop?
Several mechanisms cooperate: ligand may leave, the G alpha subunit hydrolyses its bound nucleotide, messengers are removed, targets are dephosphorylated, receptors can be phosphorylated and bound by arrestins, and receptors may internalise. The dominant step depends on timescale and receptor context.
Exam move
Draw a generic GPCR pathway without naming a specific ligand: receptor, G protein, effector, messenger, target and response. Add one shutoff mechanism beside every activation step. Then diagnose six mutants by asking for the earliest normal and earliest abnormal readout. Practise interpreting time courses rather than endpoints and distinguish synthesis from removal.
This topic sits in the stated Final Exam range, so prepare both compact mechanism chains and experimental answers with upstream, intermediate and phenotype measurements. Repeat the diagram with a sustained agonist and mark which negative controls should change first. Finally, explain how a receptor antagonist, an effector inhibitor and a messenger-degradation inhibitor create three distinguishable response traces.
Include recovery after washout and a receptor-independent positive control so failed ligand response can be separated from damage to the shared downstream machinery.
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