Signal amplification in GPCR signalling
In signal amplification, a few ligand molecules (the signalling molecules that bind a receptor) produce a relatively large cellular response.
Remember
A few occupied receptors can give a large response because each step in the chain multiplies the signal, not because the receptor stays active for longer.
Cells can react strongly to very low concentrations of a hormone. The explanation is signal amplification: a few ligand-receptor binding events give a large cellular response. It happens inside the cell, after the receptor is activated. It does not need extra ligand to arrive, and it does not need more receptors on the surface.
Amplification is achieved through a cascade, a chain of steps in which one activated protein switches on the next. A G protein-coupled receptor (GPCR, a cell-surface receptor that spans the membrane seven times) changes shape when its ligand attaches. One active receptor then switches on many G proteins (three-part switch proteins on the inner face of the membrane, holding a molecule called GDP when off and a molecule called GTP when on).
Each active G protein then switches on an effector, usually an enzyme such as adenylyl cyclase (which makes the second messenger cyclic AMP, or cAMP, from ATP). A second messenger is a small molecule that carries the message through the cell, and each enzyme can make many of them. Every step multiplies the one before it, so a few ligand molecules end in a large response.
Amplification concerns the size of the response, not how long it lasts. The signal is switched off separately: the alpha subunit (one part of the three-part G protein) slowly hydrolyses (splits) its bound GTP to GDP, and the subunits re-assemble.
Key facts
- Definition
- a few ligand molecules are enough to produce a relatively large cellular response.
- Where it happens
- inside the cell, after the receptor is activated.
- Cascade
- an activated enzyme can switch on several molecules of the next, so the signal grows at each level.
- Receptor step
- one active receptor switches on many G proteins.
- Effector enzyme step
- each effector enzyme (such as adenylyl cyclase) can make many second messengers.
- Switch-off
- the alpha subunit hydrolyses GTP to GDP and the subunits re-assemble, separately from amplification.
- Benefit
- cells can respond strongly to very low concentrations of a hormone or neurotransmitter.
Exam traps
- Slow hydrolysis of GTP by the alpha subunit does affect how long a signal lasts, but that concerns its duration and when it ends, not the size of the response, which comes from the cascade.
- Amplification does not rely on a receptor's affinity for its ligand changing. Affinity describes how tightly a receptor binds its ligand, whereas amplification multiplies the number of activated molecules after the receptor.
- A GPCR does not move into the nucleus to switch on genes, because it stays in the plasma membrane and signals through G proteins and second messengers.
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