Why do cells need to communicate?
A body has trillions of cells. They must work together. So cells send and receive signals. A signal is usually a chemical called a ligand (a small molecule that binds to a protein).
Ways cells signal
- Direct contact: neighbouring cells touch, or pass small molecules through tiny channels (gap junctions in animals, plasmodesmata in plants). Immune cells check each other by touching surface molecules.
- Local signaling: a cell releases a signal that acts on cells close by. Example: growth factors near a cut; neurotransmitters across a synapse.
- Long-distance (endocrine) signaling: hormones travel in the blood to far-away target cells. Example: insulin, adrenaline.
- Even bacteria signal: in quorum sensing they sense how many neighbours there are and act together when numbers are high.
Introduction to signal transduction: the three stages
Every signaling pathway has three stages.
- Reception: the ligand binds a receptor protein. The fit is very exact, like a key and lock. Only cells with the right receptor respond. This is why a hormone in the blood affects only its target cells.
- Transduction: binding changes the receptor's shape. This starts a chain of changes inside the cell. The message changes form (from outside chemical to inside chemical).
- Response: the cell does something: turns a gene on or off, opens an ion channel, activates an enzyme, divides, or even dies (apoptosis).
Where is the receptor?
- Membrane receptors for water-loving (polar) or large signals that cannot cross the membrane: G protein-coupled receptors (GPCRs), receptor tyrosine kinases, ligand-gated ion channels.
- Inside receptors (in the cytoplasm or nucleus) for small fat-loving signals such as steroid hormones (testosterone, oestrogen) and thyroid hormone. They pass through the membrane and the hormoneβreceptor pair acts directly on DNA.
Signal transduction pathways, second messengers and amplification
Inside the cell, the message is passed along a relay chain of proteins.
- Phosphorylation cascade: enzymes called protein kinases add a phosphate group to the next protein, which switches it on. Phosphatases remove phosphates and switch proteins off, so the signal can stop.
- Second messengers: small molecules made inside the cell that spread the message fast. The first messenger is the ligand outside. Common second messengers are cAMP (made from ATP by the enzyme adenylyl cyclase) and calcium ions (CaΒ²βΊ).
- GPCR example: adrenaline binds a GPCR β a G protein swaps GDP for GTP and turns on β adenylyl cyclase makes cAMP β cAMP activates protein kinase A β a chain of kinases β enzymes break glycogen into glucose.
- Amplification: each step switches on many molecules of the next step. One adrenaline molecule can lead to millions of glucose molecules being released.
- Changes in a pathway: a mutation in a receptor or relay protein can block a signal or leave it stuck ON. A relay protein stuck ON can make cells divide nonstop, which is one cause of cancer. Many medicines work by blocking a receptor.
Feedback: keeping the body in balance
Homeostasis means keeping conditions inside the body steady. Signaling pathways are controlled by feedback.
- Negative feedback reverses a change and brings a value back to the set point. Example: blood glucose goes up after a meal β insulin is released β cells take in glucose β glucose falls β insulin release slows. Body temperature and the thyroid hormone loop also use negative feedback.
- Positive feedback makes a change bigger until an event is finished. Example: during childbirth, oxytocin causes contractions, contractions cause more oxytocin. Blood clotting and fruit ripening (ethylene) are other examples.
If feedback fails, disease can follow. In type 1 diabetes no insulin is made; in type 2 diabetes cells stop responding well to insulin, so the negative feedback loop does not work.
Try it and exam tips
Try it: in the 3D free-play step set the signal to 3. Note the response. Tick Block receptor: the response drops to zero even though the signal is still there. This is how a receptor-blocking medicine works.
Exam tips: name all three stages in order; say whether a signal is polar (membrane receptor) or non-polar (inside receptor); explain amplification with numbers; for feedback, always say what is detected, what changes and how the change is reversed (negative) or increased (positive). Questions often ask you to predict the effect of a mutation or a blocking drug.
Key formulas and definitions
- Reception β Transduction β Response
- First messenger (ligand, outside) β receptor β second messenger (cAMP, CaΒ²βΊ, inside)
- ATP β cAMP (enzyme: adenylyl cyclase)
- Kinase adds phosphate = ON; phosphatase removes phosphate = OFF
- Negative feedback: change β opposite effect β back to set point
- Positive feedback: change β bigger change β event completed
Worked examples
1. Insulin is a protein. Testosterone is a steroid. Where is the receptor for each?
Insulin is large and polar, so it cannot cross the fat-rich membrane: its receptor is on the cell surface (a receptor tyrosine kinase). Testosterone is small and non-polar, so it passes through the membrane: its receptor is inside the cell.
2. In a pathway, 1 receptor activates 10 G proteins, each G protein makes 100 cAMP, and each cAMP-activated enzyme acts on 1,000 molecules. How many product molecules come from one signal?
Multiply each step: 1 Γ 10 Γ 100 Γ 1,000 = 1,000,000. One signal gives about one million product molecules. This is amplification.
3. A mutation makes a relay protein unable to switch off. Predict the effect.
The relay stays ON even with no signal. The response keeps happening. If the pathway tells the cell to divide, the cell divides without control, which can lead to a tumour.
4. After lunch, blood glucose rises from 5 to 8 mmol/L. Describe the feedback.
Pancreas cells sense the rise and release insulin. Insulin binds receptors on liver and muscle cells, which take in glucose and store it as glycogen. Glucose falls back towards 5 mmol/L and insulin release slows. This is negative feedback.
Common mistakes
- Thinking the signal molecule always enters the cell. Most signals stay outside and only bind a membrane receptor.
- Mixing up first and second messengers: the ligand is the first messenger; cAMP or CaΒ²βΊ inside the cell is the second.
- Saying positive feedback is 'good' and negative is 'bad'. Negative feedback keeps balance; positive feedback drives a process to completion.
- Forgetting that a cell responds only if it has the matching receptor.