Cell Signalling: Receptors, Second Messengers and Cell Responses

Figure 0. A signal arrives: glowing messenger molecules drift toward the receptors on a cell's surface. The cell that carries the right receptor hears the message; every other cell ignores it.

Level: GCSE Biology (AQA, OCR, Edexcel), A-level Biology (AQA, OCR A, Edexcel), AP Biology and IB Biology. The words are simple. The depth is full.

Your body holds about 37 trillion cells, and they are not working alone. When you run, your liver releases glucose, your heart beats faster and your lungs take in more air — all at the same moment, all because cells are talking to each other. Cell signalling (the way cells send, receive and act on chemical messages) is that conversation. One cell releases a chemical signal, another cell catches it with a receptor (a protein built to detect one specific signal), and the receiving cell changes what it does. This post teaches the whole conversation from the start: how far signals travel, the four kinds of receptor, the two great second-messenger systems, and what happens when the conversation goes wrong.

What is cell signalling, and why must cells talk?

A single cell can look after itself — a bacterium does it all the time. But a body made of trillions of cells needs coordination. Your blood glucose must stay near 5 mmol/L whether you have just eaten or just run a mile. A wound must close, which means cells near the cut must divide while cells further away stay calm. A plant must bend toward light, which means cells on the shaded side must grow faster than cells on the lit side. None of that happens by luck. It happens because cells send messages and other cells answer them.

Every signalling pathway follows the same three stages, and examiners ask about them by name. Step 1 — reception: a signalling molecule, called a ligand (a molecule that binds to a specific receptor), arrives and binds to its receptor. Step 2 — transduction: the signal is relayed and changed into a form the cell can use — usually a chain of molecules switching each other on, one after another. Step 3 — response: the cell does something: it changes an enzyme, opens a channel, moves a transporter, or switches a gene on or off. Reception, transduction, response — learn that order, because every question in this topic is really asking which stage has changed. The homeostasis lesson shows the same three stages running the body's feedback loops, and the cell membrane lesson shows where most receptors sit.

One more idea before the detail: the signal is never the whole story. The same adrenaline that makes a liver cell release glucose makes a heart cell beat faster and a blood vessel narrow. The molecule is identical in all three places — what differs is the receiving cell. Its receptors and its own internal machinery decide what the signal means. Remember that sentence; it answers more exam questions than any other in this post.

How far does a signal travel?

Signals are sorted by how far they go, and each distance has a name you must know. Direct contact (juxtacrine) signalling (messages passed between cells that touch) uses tiny channels: gap junctions (protein channels joining two animal cells) let ions and small molecules pass straight from one cell to its neighbour, and plasmodesmata (channels through plant cell walls) do the same job in plants. Heart muscle cells use gap junctions so the whole heart contracts as one.

Paracrine signalling (a signal that acts on nearby cells) is the local shout: a cell releases a messenger into the fluid around it, and only its neighbours hear it. Histamine released by damaged cells makes nearby blood vessels leaky — that is why a sting swells. Autocrine signalling (a cell signalling to itself) is a cell talking to its own receptors — some cancer cells do this, releasing growth signals that drive their own division. Synaptic signalling (a signal sent across a synapse, the tiny gap between a nerve cell and its target) is paracrine signalling with a name of its own: a neurotransmitter crosses a gap of about 20–50 nanometres in a fraction of a millisecond.

Endocrine signalling (a hormone carried in the blood to distant cells) is the long-distance call. A hormone (a chemical messenger released into the blood) such as insulin or adrenaline can reach every cell in the body — but only the cells carrying its receptor answer. Finally, pheromones (chemical signals released into the air or water) carry messages between animals of the same species, such as the scent that attracts a mate. The table below puts the five kinds side by side.

Kind of signalling	Distance	Example
Direct contact (juxtacrine)	Touching cells only	Gap junctions in heart muscle; plasmodesmata in plants
Paracrine	Nearby cells	Histamine at a sting; growth factors in a wound
Autocrine	The same cell	A T cell boosting its own activation; cancer cells driving their own growth
Synaptic	Across a synapse (~20–50 nm)	Acetylcholine at a nerve–muscle junction
Endocrine	Whole body, in the blood	Insulin, adrenaline, thyroid hormone

The distance rule also explains speed. Direct contact and synaptic signals are the fastest — milliseconds. Paracrine signals take seconds. Hormones take seconds to minutes to arrive, but they reach everywhere. And one signal can use more than one distance: adrenaline is released as a hormone into the blood, and it also acts as a neurotransmitter at some synapses. The membrane transport lesson explains how these messengers cross — or fail to cross — the membrane, which decides which receptor they use next.

What is a ligand, and why do only some cells listen?

A ligand is any molecule that carries a message by binding to a receptor. Ligands come in many shapes — small molecules such as adrenaline and acetylcholine, peptides (short chains of amino acids) such as insulin, proteins such as growth factors, and even gases such as nitric oxide. But they all share one rule: specificity (only the right ligand fits a given receptor). A receptor is a protein folded into a pocket that matches its ligand the way a lock matches one key. Adrenaline cannot switch on an insulin receptor, and insulin cannot switch on an adrenaline receptor, because the shapes do not fit. That is also why drugs work: a drug that fits a receptor can switch it on (an agonist, a molecule that mimics the natural signal) or block it (an antagonist, a molecule that sits in the receptor and stops the real signal binding). Beta blockers, which slow the heart, are antagonists of adrenaline's beta receptors.

Whether a ligand can even reach its receptor depends on one property: can it cross the fatty cell membrane? Hydrophilic ligands (water-soluble signals, such as adrenaline, insulin and acetylcholine) cannot cross the lipid bilayer, so they must bind receptors on the cell surface. Hydrophobic ligands (lipid-soluble signals, such as steroid hormones and thyroid hormone) dissolve straight through the membrane and meet their receptors inside the cell. That single difference splits the whole topic in two: surface receptors for water-soluble signals, and intracellular receptors for fat-soluble ones. The ethylene lesson shows a gas that slips through membranes in plants, and the auxin lesson shows a plant signal that works through its own receptors.

Two more words examiners use. A target cell (a cell that carries the receptor for a signal) is any cell that can answer a given signal — a liver cell is a target cell for adrenaline and for insulin, but a red blood cell, which has no nucleus and almost no receptors, is a target for almost nothing. And a signal can be amplified (made bigger at each step of the relay), so that one ligand binding one receptor ends up changing millions of molecules — the subject of the next-but-one section, and the most impressive number in this whole post.

The four kinds of receptor — one signal, four doors

Every receptor in the body belongs to one of four kinds. Learn them as a set, because exam questions love to ask which kind a named signal uses — and the answer always follows from whether the ligand can cross the membrane and how fast the response must be.

Figure 1. The four kinds of receptor. The ligand's chemistry decides the door: fat-soluble signals walk through the membrane to an intracellular receptor, while water-soluble signals must knock on a surface receptor.

1. Intracellular receptors sit in the cytoplasm or the nucleus and wait for fat-soluble ligands — steroid hormones such as cortisol, oestrogen and testosterone, and thyroid hormone. The ligand slips through the membrane, binds the receptor, and the pair moves to the DNA, where it switches genes on or off. The response is slow (hours) because new proteins must be made, but it lasts a long time. Cortisol raising blood glucose during stress is the classic example.

2. Ion channel-linked receptors are channels with a ligand-binding site. When the ligand binds, the channel opens and ions rush through — sodium in, potassium out, or chloride in. Acetylcholine at the nerve–muscle junction opens sodium channels, and the rush of sodium triggers the muscle to contract. This is the fastest receptor of all: milliseconds, because nothing needs to be made and no chain of enzymes is involved. The cell division lesson shows where ion flows matter in the cell cycle, and the cell organelles lesson shows the membranes these channels sit in.

3. G protein-coupled receptors (GPCRs) are the most common receptors in the body — humans have about 800 of them, and about 30% of prescription drugs target them. A GPCR is one protein chain that threads through the membrane seven times. When the ligand binds outside, the receptor changes shape inside and switches on a G protein (a molecular switch that is ON when it holds GTP and OFF when it holds GDP). The G protein then switches on an enzyme — most often adenylyl cyclase, which makes cAMP. Adrenaline, glucagon, histamine and many neurotransmitters all use GPCRs.

4. Receptor tyrosine kinases (RTKs) come in two halves. When the ligand binds, the halves join together, and each half adds phosphate groups to tyrosine amino acids on the other half — a step called autophosphorylation (a receptor adding phosphate to itself). Those phosphates are docking sites for relay proteins, which carry the signal on. Insulin, epidermal growth factor (EGF) and platelet-derived growth factor all use RTKs. RTKs control growth and division, which is why broken RTKs are found in many cancers.

Receptor kind	Ligand	Speed	Example
Intracellular	Steroids, thyroid hormone	Hours	Cortisol switching genes on
Ion channel-linked	Acetylcholine, GABA, glycine	Milliseconds	Muscle contraction at a synapse
GPCR	Adrenaline, glucagon, histamine	Seconds	Adrenaline releasing glucose
Receptor tyrosine kinase	Insulin, EGF, PDGF	Minutes	Insulin moving GLUT4 to the membrane

How does a GPCR work? Adrenaline, step by step

The adrenaline pathway is the most examined signalling pathway in biology, so learn it as a numbered chain. You are running from danger. Your adrenal glands release adrenaline into the blood. A liver cell carries beta receptors — GPCRs — on its surface. Here is what happens, step by step.

Step 1 — binding. Adrenaline binds the beta receptor on the outside of the liver cell. The receptor changes shape.

Step 2 — the G protein switches on. The changed receptor meets a G protein (called Gs, the "s" meaning it stimulates) sitting on the inner face of the membrane. The G protein drops its GDP and picks up GTP — and the GTP-bound form is the active one. The G protein splits into two parts, and the alpha part swims along the membrane to find its target enzyme.

Step 3 — adenylyl cyclase makes cAMP. The active G protein switches on adenylyl cyclase (the enzyme that converts ATP into cyclic AMP). Each cyclase makes about 100 cAMP molecules. cAMP is the second messenger (a small molecule made inside the cell that carries the signal on) — the first messenger was adrenaline outside, and cAMP is the second messenger inside.

Step 4 — PKA switches on. cAMP binds protein kinase A (PKA) (an enzyme that adds phosphate groups to proteins) and switches it on. PKA is a kinase (an enzyme that transfers a phosphate group from ATP onto a protein), and adding a phosphate usually switches the target protein on or off.

Step 5 — the kinase chain. PKA phosphorylates phosphorylase kinase, which phosphorylates glycogen phosphorylase, which cuts glucose molecules off glycogen (the animal starch stored in liver and muscle). Each step activates many copies of the next enzyme — and that multiplication is the whole point of the cascade. The bioenergetics MCQs show what the cell then does with that glucose, and the bioenergetics quiz tests the ATP accounting behind it.

Notice what the pathway does NOT do: adrenaline never enters the cell. It never needs to. The receptor, the G protein, the cyclase, the cAMP and the kinases do all the work inside, while adrenaline stays outside and is later removed from the blood. That is the meaning of signal transduction: a message crosses a membrane it cannot itself cross.

Signal amplification — one molecule, 100 million answers

The most surprising number in cell biology is how far one signal goes. Follow the adrenaline chain in Figure 2 and count with it: one adrenaline molecule switches on about 100 G proteins. Those switch on adenylyl cyclase, which makes about 10,000 cAMP molecules. The cAMP switches on about 10,000 PKA molecules. Each PKA phosphorylates about 10 phosphorylase kinase molecules — about 100,000 of them. Each of those activates about 10 glycogen phosphorylase molecules — about 1,000,000. And each phosphorylase releases many glucose molecules from glycogen — about 100,000,000 (10⁸) glucose molecules in total. One signal, one hundred million answers.

Figure 2. Signal amplification in the adrenaline pathway. Each step multiplies the signal — that is why a whisper of hormone can empty a liver of glucose in seconds.

Amplification works because every step is an enzyme: one enzyme can act on many copies of the next molecule, and the next enzyme can act on many more. The same trick appears in blood clotting, in the immune system and in vision — one photon of light can close hundreds of sodium channels in a rod cell. But amplification has a price: a small error early in the chain becomes a huge error at the end, which is why the cell also needs strong off-switches (section 11). Watch the cascade happen one step at a time.

Watch it move — adrenaline releases glucose in 5 steps

Adrenaline arrives at a liver cell — the signal. One molecule, one receptor, and a whole liver about to answer.

Follow the numbers in the animation: 1 → 100 → 10,000 → 100,000 → 100,000,000. If you can walk through those five steps, you can answer any amplification question: name the step, name the molecule, and give the number. The common error is calling cAMP the first messenger — it is the second; adrenaline is the first.

The second messenger system: IP3, DAG and calcium

cAMP is not the only second messenger. Some GPCRs use a different G protein (Gq) and a different enzyme, and the result is two messengers made from one cut in the membrane itself. This pathway runs vasopressin (the hormone that saves water), adrenaline on alpha-1 receptors (which narrow blood vessels), and many signals in the brain.

Figure 3. The IP3 / DAG pathway. One cut in the membrane makes two messengers — IP3, which fetches calcium, and DAG, which stays behind to switch on protein kinase C.

Step 1. The ligand binds a GPCR linked to a Gq protein, which switches on phospholipase C (the enzyme that cuts a membrane lipid called PIP2).

Step 2. Phospholipase C cuts PIP2 (phosphatidylinositol bisphosphate, a lipid in the inner face of the membrane) into two pieces: IP3 (inositol trisphosphate, a small water-soluble molecule) and DAG (diacylglycerol, a fatty molecule that stays in the membrane).

Step 3. IP3 travels through the cytoplasm to the endoplasmic reticulum (the cell's internal store of calcium), where it opens calcium channels. Calcium floods out: the cytoplasmic level rises from about 0.1 micromoles per litre to about 1–10 micromoles per litre — a 10- to 100-fold rise.

Step 4. Calcium binds calmodulin (the cell's calcium-sensing protein), and the calcium–calmodulin pair switches on enzymes. Meanwhile DAG, still sitting in the membrane, switches on protein kinase C — helped by the same calcium. Two arms, one signal, one coordinated response: a muscle contracts, a gland secretes, a cell divides.

Why keep calcium so low in a resting cell? Because a messenger only works if its background is quiet. At 0.1 micromoles per litre, a ten-fold rise is unmistakable — and it has to be, because calcium switches on powerful enzymes that must not run all the time. The ER stores calcium at high concentration, the cell pumps it back in after the signal, and the level falls again. If calcium stayed high, the cell would die — which is why calcium overload kills cells in a stroke and a heart attack. The membrane transport lesson covers osmosis and ion balance, and the cytoskeleton lesson shows what calcium does to the cell's moving parts.

Insulin and the RTK: opening the glucose door

Insulin is the hormone that lowers blood glucose after a meal, and it works through a receptor tyrosine kinase — the fourth kind of receptor, and a completely different mechanism from adrenaline's GPCR.

Figure 4. Insulin opens the glucose door. The receptor adds phosphate to itself, a relay of three proteins carries the message, and GLUT4 transporters move to the surface — the whole job takes minutes.

Step 1 — binding and joining. Insulin binds the outside of its receptor, and the receptor's two halves join together.

Step 2 — autophosphorylation. Each half adds phosphate groups to tyrosine residues on the other half. Those phosphates are docking sites — handles that the next proteins can grip.

Step 3 — the relay. A protein called IRS (insulin receptor substrate) docks and is phosphorylated, then PI3K (phosphoinositide 3-kinase) is switched on, then Akt (also called protein kinase B) is switched on. IRS → PI3K → Akt is the chain to memorise.

Step 4 — GLUT4 moves. Akt sends the signal that moves vesicles full of GLUT4 (a glucose transporter protein) to the cell surface, where they fuse with the membrane. GLUT4 doors appear in the membrane, glucose rushes into muscle and fat cells, and blood glucose falls back toward 5 mmol/L.

In type 2 diabetes, the insulin is there and the receptors are there — but the cells answer weakly. This is insulin resistance (cells responding poorly to insulin): the relay is blunted, fewer GLUT4 doors reach the surface, and glucose stays in the blood. It is a signalling disease, not a hormone shortage — and it is the mirror image of type 1 diabetes, where the insulin itself is missing. The homeostasis lesson covers the insulin–glucagon feedback loop that keeps blood glucose steady, and the plant body lesson shows where glucose is made and stored in plants.

Steroid hormones: slow signals that change genes

Steroid hormones work differently from every signal so far, and the difference is the whole point. Cortisol, oestrogen, testosterone and aldosterone are all made from cholesterol, so they are hydrophobic — they dissolve through the fatty membrane and meet their receptor inside the cell, in the cytoplasm or the nucleus.

The hormone–receptor pair then binds to DNA and changes which genes are read. That is why the response takes hours: the cell must make new mRNA, then new protein, before anything changes. But the change lasts for hours or days, because the new proteins stay. Cortisol released during stress switches on genes that raise blood glucose and damp down the immune system. Oestrogen switches on genes that build the uterus lining. The pill works the same way: synthetic hormones switch genes on and off in the ovaries and uterus.

Compare the four receptor kinds by speed and you have a table for the exam: ion channels in milliseconds, GPCRs in seconds, RTKs in minutes, intracellular receptors in hours. The question "why does this response take so long?" is always answered by the mechanism — and for steroids, the mechanism is gene expression. The cytokinin lesson and the gibberellin lesson show plant hormones that also change gene expression, and the cell division lesson shows the genes that control when a cell divides.

Synapses: acetylcholine and the fastest signals

The fastest signalling in the body happens at synapses, and it uses the fastest receptor — the ion channel-linked receptor. When a nerve impulse reaches the end of a motor neurone, the neurone releases acetylcholine (a neurotransmitter) into the synaptic cleft, the gap of about 20–50 nanometres between the nerve ending and the muscle fibre.

Acetylcholine binds receptors on the muscle membrane. The channels open, sodium rushes in, and the muscle membrane depolarises — an end-plate potential that triggers the muscle to contract. The whole event takes a few milliseconds. Then acetylcholinesterase (the enzyme that breaks down acetylcholine) splits the acetylcholine in under a millisecond, the channels close, and the muscle relaxes, ready for the next impulse. One nerve impulse, one brief twitch — that is the precision the system is built for.

Block acetylcholinesterase and the precision collapses: acetylcholine lingers, the channels stay open, and the muscle cannot relax. That is how nerve gases and some insecticides kill, and — in tiny, controlled doses — how drugs for myasthenia gravis help, by giving a weak signal more time to work. The same acetylcholine system runs the heart, the gut and the brain, which is why the same drug can slow a heart and sharpen a memory. The cell cycle lesson shows how signals like these decide whether a cell divides at all.

How does a signal switch off?

A signal that cannot be switched off is worse than no signal at all. Every pathway has off-switches at every stage, and examiners ask about them as often as they ask about switching on.

• The ligand is removed. Enzymes destroy it (acetylcholinesterase splits acetylcholine), transporters pump it back into cells (serotonin reuptake), or the blood simply carries it away (adrenaline is cleared by the liver).
• The receptor is desensitised. After long exposure, receptors are pulled inside the cell (downregulation) or chemically switched off — which is why a drug's effect fades with time and why caffeine stops working if you drink it all day.
• The G protein switches itself off. It slowly splits its GTP back to GDP, and the active form ends. Cholera toxin breaks this off-switch, which is why cholera is deadly.
• The second messenger is destroyed. Phosphodiesterase converts cAMP to AMP. Calcium is pumped back into the ER or out of the cell, and the level falls to 0.1 micromoles per litre again.
• The phosphates are removed. Phosphatases (enzymes that remove phosphate groups) undo what kinases did, switching each relay protein back off. Kinases and phosphatases are a pair: one writes, the other erases.

Notice the pattern: every "on" has an "off", and the balance between them sets the strength of the response. Drugs exploit this balance from both sides — some switch signals on, some stop the off-switches. The specific immunity lesson shows the same balance in immune cells, where a signal must be switched off or the immune system attacks the body itself.

When signalling goes wrong

Signalling pathways are so central that most diseases are signalling diseases. Learn four of them — each one teaches a different stage of the pathway.

Cancer — a stuck growth signal. Growth factors normally tell cells to divide through RTKs and the Ras relay. Ras (a small G protein in the growth pathway) passes the "divide" signal on, then switches itself off. A mutation that leaves Ras stuck ON means the cell divides without any signal — and Ras mutations are found in about 30% of human cancers, about 1 in 3. Other cancers overproduce RTKs: HER2-positive breast cancer makes far too many HER2 receptors, so the growth signal is always loud. The drug Herceptin blocks HER2, and it works precisely because the disease is a signalling disease.

Cholera — a stuck G protein. Cholera toxin locks the Gs protein in its ON state, so adenylyl cyclase keeps making cAMP without any signal. Gut cells flood with cAMP, chloride and water pour out, and the patient loses litres of water a day. The cure is mostly water and salts — replacing what the broken signal drove out.

Diabetes — a blunted relay. In type 2 diabetes the insulin relay is blunted, so GLUT4 doors do not reach the surface and glucose stays in the blood. In type 1 diabetes the insulin itself is missing. Both raise blood glucose, but for opposite reasons — and that is why the treatments differ.

Myasthenia gravis — attacked receptors. The immune system attacks the acetylcholine receptors on muscle, so fewer receptors are left to hear the nerve's signal. Muscles weaken with use and recover with rest. Drugs that block acetylcholinesterase give the remaining signal more time to work, and the muscle answers better.

Drugs are signalling tools. Beta blockers block adrenaline's receptors and slow the heart. Phosphodiesterase blockers stop cAMP being destroyed, so the signal lasts longer — caffeine does this mildly, which is why it keeps you alert. Antihistamines block histamine's receptors, so the paracrine signal that makes you sneeze is never heard. Learn the pathway and the drug explains itself.

Five common mistakes

1. Calling cAMP the first messenger. The first messenger is the hormone outside the cell (adrenaline). cAMP is the second messenger, made inside. The exam will offer cAMP as the first messenger — it is not.
2. Saying the response depends only on the signal. The same adrenaline gives different responses in liver and heart. The receptor and the target cell's machinery decide the response, not the signal alone.
3. Mixing up the receptor types. Steroids use intracellular receptors, acetylcholine at a synapse uses ion channels, adrenaline uses GPCRs, insulin uses RTKs. If you know the ligand, you can work out the receptor — and the speed follows from the receptor.
4. Forgetting that amplification needs off-switches. A cascade that multiplies 100-million-fold must be switched off, or the cell would never stop responding. Phosphodiesterase, phosphatases and GTP splitting are part of the answer, not decoration.
5. Saying a mutation in a receptor has no effect if the signal is still made. The pathway is a chain: break any link — receptor, G protein, enzyme, relay — and the response changes. A broken receptor means no response even when the hormone is present in large amounts.

How to answer a 6-mark question

Exam questions on this topic follow one pattern: a drug or mutation hits one step, and you must predict what happens downstream. Step 1: name the pathway and its order (reception → transduction → response). Step 2: name the step that is hit and say what it normally does. Step 3: walk downstream, step by step, saying what increases and what decreases. Step 4: state the final response. Step 5: name the off-switch or the reason the effect is limited.

Model paragraph (6 marks). A drug blocks adenylyl cyclase in liver cells. Explain why blood glucose falls. "Adrenaline normally binds beta receptors (GPCRs) on liver cells, switching on Gs proteins, which activate adenylyl cyclase to make cAMP from ATP. cAMP switches on PKA, which switches on phosphorylase kinase and glycogen phosphorylase, releasing glucose from glycogen. If adenylyl cyclase is blocked, no cAMP is made, so PKA stays off, the kinase chain never runs, and glycogen is not broken down. Less glucose enters the blood, so blood glucose falls — and the effect is limited because glucagon uses the same pathway, so it is blocked too."

FAQs — cell signalling

What is the difference between a first messenger and a second messenger? The first messenger is the signal outside the cell — a hormone or neurotransmitter. The second messenger is a small molecule made inside the cell when the receptor is activated — cAMP, IP3 or calcium ions. The first messenger never enters the cell; the second messenger carries the message inside.

Why do cells need receptors at all — why can't signals just enter the cell? Most signals are water-soluble and cannot cross the fatty membrane, so they need a receptor to carry the message across. And receptors give specificity: only cells with the right receptor hear the signal, so one hormone can do different jobs in different tissues.

What is the difference between a kinase and a phosphatase? A kinase adds a phosphate group to a protein (usually switching it on or off); a phosphatase removes a phosphate group, undoing the kinase's work. Every step in a signalling cascade has both — one writes, the other erases.

How can one adrenaline molecule cause such a big response? Amplification: each step in the cascade activates many copies of the next step. One adrenaline → about 100 G proteins → 10,000 cAMP → 10,000 PKA → 100,000 phosphorylase kinase → 1,000,000 glycogen phosphorylase → about 100 million glucose molecules.

Why is calcium kept so low inside a resting cell? So that a rise is a clear signal. At 0.1 micromoles per litre, a ten-fold rise is unmistakable — and calcium switches on powerful enzymes that must not run all the time. The ER stores calcium so the flood is ready when IP3 calls for it.

Do plants use cell signalling too? Yes — plant hormones such as auxin, gibberellin, cytokinin and ethylene are all signals with receptors, and plants use calcium as a second messenger just as animals do. The molecules differ, but the logic — signal, receptor, relay, response — is the same in every living thing.

Sources

• AP Biology Course and Exam Description, Unit 4 Cell Communication and Cell Cycle, Topics 4.1–4.4 — College Board AP Central
• AQA A-level Biology specification 7402, §3.2 Cells and §3.6 Organisms respond to changes in their environments — aqa.org.uk
• AQA GCSE Biology specification 8461, §5.2 Homeostasis and §5.3 Hormones in humans — aqa.org.uk
• OpenStax Biology 2e, Chapter 9 Cell Communication — openstax.org
• OpenStax Biology 2e, §9.1 Signaling molecules and cellular receptors — openstax.org
• IB DP Biology Guide 2023, C2.1 Chemical signalling (HL) and C2.2 Neural signalling — ibo.org

Continue learning

• Cell Membrane Structure — the membrane the receptors sit in: phospholipid bilayer, fluid mosaic model, membrane proteins.
• Membrane Transport: How Substances Cross Cell Membranes — diffusion, facilitated diffusion, active transport and the channels that ions use.
• Homeostasis: Receptors, Effectors & Feedback Explained — the same receptors running the body's feedback loops, including insulin and glucagon.
• Cell Division: Mitosis, Meiosis and the Cell Cycle — how growth-factor signals decide whether a cell divides, and what happens when the signal sticks on.
• Microscopy and Cell Size: How Microscopes Reveal Cells — how we first saw the cells that do all this talking.
• Bioenergetics MCQs: ATP, Respiration, Photosynthesis and Energy Flow — what the cell does with the glucose that adrenaline releases.
• Introduction to Ethylene: A Gaseous Plant Hormone — a plant signal that slips through membranes, like a steroid hormone in animals.

20 Explained MCQs — answers hidden until opened

Open each question to reveal its answer and explanation. The interactive quiz below uses a different set of questions.

1. What is cell signalling?

A. Communication between cells using chemical signals, so the body can coordinate its activities   B. The transport of glucose across the cell membrane   C. The division of one cell into two identical daughter cells   D. The movement of cells from one place to another in the body
Answer: A. Cell signalling is how cells talk to each other. One cell releases a chemical signal, another cell detects it with a receptor, and the receiving cell changes what it does — so millions of cells can act together instead of each doing its own thing.

2. Which of these is direct-contact signalling, where two cells must touch?

A. Gap junctions in animals and plasmodesmata in plants   B. Insulin travelling in the blood to muscle cells   C. Adrenaline travelling in the blood to the heart   D. A pheromone drifting through the air to another animal
Answer: A. Gap junctions are tiny channels joining two animal cells, and plasmodesmata are channels through plant cell walls. Signals pass straight from one cell to its neighbour — no travelling through blood or air is needed.

3. Which type of signal travels the furthest in the body?

A. A juxtacrine signal — passed by direct contact between cells   B. An endocrine signal — a hormone carried in the blood to distant target cells   C. A paracrine signal — released to act on nearby cells only   D. An autocrine signal — a cell signalling to itself
Answer: B. Endocrine signals are hormones: they enter the blood and can reach cells far away from where they were released. Paracrine signals act only on neighbours, autocrine signals act on the cell that released them, and juxtacrine signals need direct contact.

4. What is a ligand?

A. A fat molecule that stores energy in the liver   B. A channel that lets ions cross the cell membrane   C. A signalling molecule that binds to a specific receptor protein   D. A protein that copies DNA into RNA inside the nucleus
Answer: C. A ligand is any molecule that carries a message by binding to a receptor — a hormone, a neurotransmitter or a growth factor. The binding is specific, like a key fitting one lock, and it is the binding that starts the response.

5. Adrenaline is released into the blood and reaches every cell in the body. Why do only some cells respond to it?

A. Adrenaline can only enter cells that are dividing   B. Adrenaline is destroyed before it reaches most cells   C. Adrenaline only works on cells in the heart and liver   D. Only target cells carry the adrenaline receptor — cells without it cannot detect the signal
Answer: D. A signal is only heard by cells that carry its receptor. Adrenaline floods the whole body, but a skin cell without beta receptors ignores it, while a liver cell with beta receptors breaks down glycogen. The receptor, not the signal, decides who responds.

6. What are the three stages of a signal transduction pathway, in order?

A. Response, reception, transduction   B. Reception, transduction, response   C. Reception, response, transduction   D. Transduction, reception, response
Answer: B. First the receptor receives the signal (reception), then the signal is relayed and changed into a form the cell can use (transduction), and finally the cell does something (response). Every pathway in this lesson follows that same three-step order.

7. A steroid hormone such as cortisol reaches a cell. Which kind of receptor does it use?

A. A G protein-coupled receptor in the membrane   B. A receptor tyrosine kinase in the membrane   C. An ion channel-linked receptor in the membrane   D. An intracellular receptor, inside the cytoplasm or nucleus
Answer: D. Steroid hormones are made from lipids, so they dissolve through the fatty membrane and meet their receptor inside the cell. The receptor-hormone pair then switches genes on or off — which is why steroid effects take hours but last a long time.

8. Which type of receptor gives the fastest response, in milliseconds?

A. An ion channel-linked receptor   B. An intracellular receptor   C. A receptor tyrosine kinase   D. A G protein-coupled receptor
Answer: A. When acetylcholine binds an ion channel-linked receptor, the channel opens at once and ions rush in — that is why a nerve signal reaches a muscle in milliseconds. GPCRs and RTKs need multi-step cascades, and intracellular receptors need new proteins to be made, so both are much slower.

9. Adrenaline binds to a G protein-coupled receptor on a liver cell. What does the receptor do first?

A. It opens a channel and lets sodium ions rush in   B. It moves into the nucleus and switches on genes   C. It changes shape and switches on a G protein inside the cell   D. It adds phosphate groups to itself
Answer: C. A GPCR is a seven-pass membrane protein. When adrenaline binds outside, the receptor changes shape inside the cell and switches on a G protein — the G protein swaps GDP for GTP and goes on to activate adenylyl cyclase. Opening a channel is the ion channel receptor's job, and adding phosphate is the RTK's job.

10. What does adenylyl cyclase make, and from what?

A. Calcium ions from the endoplasmic reticulum   B. Cyclic AMP (cAMP) from ATP   C. ATP from cyclic AMP (cAMP)   D. Glucose from glycogen
Answer: B. Adenylyl cyclase is the enzyme that turns ATP into cyclic AMP. cAMP is the second messenger: it spreads through the cell and switches on protein kinase A, which carries the signal further down the cascade.

11. What is a second messenger?

A. A second hormone released when the first hormone runs out   B. A receptor that binds two different hormones at once   C. A protein that carries a hormone through the blood   D. A small molecule made inside the cell that carries the signal on after the first messenger binds outside
Answer: D. The first messenger is the hormone outside the cell. The second messenger — cAMP, IP3 or calcium ions — is made inside the cell when the receptor is activated, and it spreads the message to the cell's machinery. One first messenger can make many second messengers, which is how the signal is amplified.

12. One adrenaline molecule binds to a liver cell. About how many glucose molecules can be released from glycogen as a result?

A. About 100 million (10^8)   B. Exactly 1 — one signal gives one glucose   C. About 100   D. About 10
Answer: A. The cascade multiplies at every step: about 100 G proteins, 10,000 cAMP, 10,000 PKA, 100,000 phosphorylase kinase and 1,000,000 glycogen phosphorylase — ending with about 100 million glucose molecules from a single adrenaline molecule. That is signal amplification.

13. What does phosphodiesterase do in the cAMP pathway?

A. It opens calcium channels in the endoplasmic reticulum   B. It switches on protein kinase A   C. It makes cAMP from ATP   D. It breaks cAMP down to AMP, switching the signal off
Answer: D. Every signal must be switched off, or the cell would never stop responding. Phosphodiesterase converts cAMP into AMP, which cannot activate PKA — so the cascade stops. Drugs that block phosphodiesterase make the cAMP signal last longer.

14. What does IP3 (inositol trisphosphate) do inside the cell?

A. It opens calcium channels in the endoplasmic reticulum, releasing Ca2+ into the cytoplasm   B. It makes cAMP from ATP   C. It switches genes on in the nucleus   D. It opens sodium channels in the cell membrane
Answer: A. IP3 is made when phospholipase C cuts the membrane lipid PIP2. IP3 travels through the cytoplasm to the endoplasmic reticulum, where it opens calcium channels — and the flood of Ca2+ is itself a second messenger that switches on enzymes.

15. Where does DAG (diacylglycerol) stay, and what does it switch on?

A. It travels to the nucleus and switches genes on   B. It stays in the membrane and switches on protein kinase C, together with Ca2+   C. It leaves the cell and acts as a hormone   D. It is stored in the endoplasmic reticulum and released later
Answer: B. When PIP2 is cut, it gives two messengers: IP3, which leaves, and DAG, which stays in the membrane. DAG plus the Ca2+ released by IP3 switch on protein kinase C — so one cut produces two arms of the same response.

16. In a resting cell, calcium in the cytoplasm is about 0.1 micromoles per litre. What happens to it when IP3 acts?

A. It falls to zero   B. It stays at 0.1 micromoles per litre   C. It rises to about 1–10 micromoles per litre — a 10- to 100-fold rise   D. It rises to about 1000 micromoles per litre
Answer: C. Cells keep cytoplasmic calcium very low on purpose, so a small rise is a loud, clear signal. When IP3 opens the ER channels, calcium floods out and rises 10 to 100 times — enough to switch on calmodulin and the enzymes that depend on it.

17. The insulin receptor is which type of receptor?

A. An ion channel-linked receptor   B. A G protein-coupled receptor   C. A receptor tyrosine kinase   D. An intracellular receptor
Answer: C. The insulin receptor is a receptor tyrosine kinase: insulin joins its two halves together, and each half adds phosphate groups to the other — autophosphorylation. That starts the relay (IRS, PI3K, Akt) that moves GLUT4 transporters to the membrane.

18. When insulin signalling works, what moves to the surface of muscle and fat cells?

A. Glycogen granules, so glucose can be stored outside the cell   B. Insulin receptors, so more insulin can bind   C. Sodium channels, so sodium can rush in   D. GLUT4 glucose transporters, so glucose can rush in
Answer: D. GLUT4 is a glucose transporter that normally sits in vesicles inside the cell. Insulin signalling makes those vesicles fuse with the membrane, putting GLUT4 doors in place — and glucose rushes in, bringing blood glucose back down.

19. What does acetylcholinesterase do at a synapse?

A. It makes acetylcholine from choline and acetate   B. It opens the acetylcholine receptor channel   C. It breaks down acetylcholine in the synaptic cleft, ending the signal   D. It carries acetylcholine across the synaptic cleft
Answer: C. Acetylcholine must be cleared the moment its job is done, or the muscle would keep contracting. Acetylcholinesterase splits it in under a millisecond, so each nerve impulse gives one brief twitch — and the next impulse can be heard cleanly.

20. Cholera toxin locks the Gs protein in its ON state. What happens next?

A. The insulin receptor stops responding to insulin   B. Calcium channels in the endoplasmic reticulum close permanently   C. Adenylyl cyclase stops working, so no cAMP is made at all   D. Adenylyl cyclase keeps making cAMP, so gut cells lose litres of water a day
Answer: D. Gs is the G protein that switches on adenylyl cyclase. Cholera toxin locks it ON, so cAMP floods the gut cells, chloride and water pour out of them, and the patient loses litres of water a day — the diarrhoea that makes cholera deadly.

Separate Interactive Quiz — 20 different questions

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