Cell Signalling

Spec Mapping: This lesson is mapped to OCR H420 Module 2.1.5 — Biological membranes (refer to the official OCR H420 specification document for exact wording). It develops the roles of membranes in cell signalling — receptor proteins as integral glycoproteins, hormones vs neurotransmitters, second messengers, and amplification.

Cells in multicellular organisms must coordinate their activities: hormones must reach their targets, neurones must tell muscles to contract, and immune cells must respond to infection at specific sites. The system that achieves this is cell signalling, and it depends on the membrane proteins introduced in Lesson 1. This lesson develops the OCR H420 Module 2.1.5 content on the roles of membranes in cell signalling.

1. What Is Cell Signalling?

Key Definition — Cell Signalling: The processes by which cells communicate with each other, using signalling molecules (such as hormones and neurotransmitters) that are released by one cell and detected by receptor proteins on or in a target cell, producing a specific response.

Signalling allows cells to coordinate function across a whole organism. It is the reason a glucose meal causes insulin release; the reason a stubbed toe produces pain; the reason a wound triggers inflammation.

2. The Basic Cell Signalling Pathway

Any signalling pathway has three common stages:

Reception — the signal molecule (ligand) binds to a specific receptor on or in a target cell.
Transduction — the signal is converted into a cellular response, often via a cascade of intracellular events.
Response — the cell changes its behaviour: gene expression, enzyme activity, secretion, movement, division.

graph LR
  A["Signalling cell<br/>releases ligand"] --> B[Ligand travels]
  B --> C[Target cell receptor]
  C --> D[Signal transduction]
  D --> E[Cellular response]

For a signalling pathway to work cleanly, three conditions are essential:

Specificity — only target cells with the correct receptor respond.
Amplification — a small signal can produce a large response via cascades.
Termination — signals must be switched off (ligand removal, receptor internalisation, enzyme degradation) so that cells can respond again.

3. Receptors and Specificity

Receptor proteins are typically membrane-bound glycoproteins — intrinsic proteins that span the plasma membrane. Their extracellular domain has a specific shape that binds only to a particular ligand; the intracellular domain initiates the response inside the cell.

Specificity means that:

Only cells with the correct receptor are affected. For example, insulin circulates through the whole body, but only cells expressing the insulin receptor (such as liver, muscle and fat cells) respond.
A single cell can carry many different receptors and so respond to several signals simultaneously.
Changing receptor numbers (up-regulation or down-regulation) is a way of adjusting a cell's sensitivity to a signal.

Exam Tip: When asked "why do only certain cells respond to a hormone?", the answer is "because only those cells have the specific receptor for that hormone".

4. Types of Signalling Molecules

Several types are examinable at A-Level:

4.1 Hormones

Hormones are chemical messengers produced by endocrine glands and transported in the bloodstream to distant target cells. Examples:

Insulin — from the pancreas; signals liver and muscle cells to take up glucose and store it as glycogen.
Glucagon — from the pancreas; signals liver cells to break glycogen down to glucose.
Adrenaline (epinephrine) — from the adrenal medulla; triggers the "fight or flight" response.
ADH (antidiuretic hormone) — from the posterior pituitary; signals kidney collecting ducts to reabsorb water.

Most protein hormones (e.g. insulin, glucagon, ADH) are water-soluble and cannot cross the phospholipid bilayer. They bind to membrane-bound receptors. In contrast, steroid hormones (e.g. oestrogen, testosterone, cortisol) are lipid-soluble and can cross the membrane to bind receptors inside the cell.

4.2 Neurotransmitters

Neurotransmitters are short-range signals released at synapses by presynaptic neurones, crossing a narrow synaptic cleft and binding to receptors on the postsynaptic membrane. Examples include:

Acetylcholine (ACh) — at the neuromuscular junction, binds to ligand-gated ion channels (nicotinic ACh receptors) on muscle fibres.
Noradrenaline — in the sympathetic nervous system.
Dopamine, serotonin, GABA, glutamate — in the brain.

Neurotransmitter signalling is fast and localised: the distance is tiny, the response is nearly instantaneous, and the neurotransmitter is rapidly broken down or taken back up.

4.3 Local Chemical Mediators

Some signalling molecules act over short distances without entering the blood. These include histamine (released in inflammation), prostaglandins and cytokines. They are important in wound healing and immune responses.

4.4 Direct Cell-Cell Contact

Cells also signal by direct contact — for example, antigen-presenting cells showing peptides to T-cells during an immune response, or plasmodesmata linking plant cells.

5. Signal Transduction — Two Example Mechanisms

Signalling molecules that cannot enter the cell must have their message "transduced" — converted into an intracellular signal. A full treatment of G-protein and kinase cascades is beyond A-Level, but you should understand two concepts.

5.1 Secondary Messengers

When a hormone such as adrenaline binds to its receptor on a liver cell, the receptor activates an enzyme (adenylyl cyclase) on the inside of the membrane. This enzyme converts ATP into cyclic AMP (cAMP), a small molecule that diffuses through the cytoplasm and activates other enzymes, which then activate still others. cAMP is a "second messenger" — it amplifies the original signal enormously. One adrenaline molecule can trigger the release of millions of glucose molecules from stored glycogen.

5.2 Enzyme Cascades and Amplification

A signalling pathway is often a cascade: the receptor activates enzyme A, which activates many copies of enzyme B, each of which activates many copies of enzyme C, and so on. Each step multiplies the signal, so a tiny extracellular concentration of hormone can produce a large cellular response. This is why hormones work at nanomolar concentrations in the blood.

graph TD
  A[1 adrenaline molecule] --> B[Activates receptor]
  B --> C[Activates ~100 G-protein and adenylyl cyclase]
  C --> D[Produces ~1000 cAMP molecules]
  D --> E[Activates ~10,000 protein kinases]
  E --> F[Phosphorylates ~100,000 glycogen phosphorylase molecules]
  F --> G[Releases ~1,000,000 glucose molecules]

6. The Specific Role of the Cell Membrane in Signalling

The plasma membrane is central to signalling in several ways:

Receptor location — receptors are intrinsic membrane proteins that span the bilayer so that the ligand-binding site is on the outside and the signalling machinery is on the inside.
Compartmentalisation — the membrane keeps intracellular signalling enzymes (like adenylyl cyclase) on the cytoplasmic side so that the signal only affects the inside of the cell.
Fluid mosaic behaviour — receptors move laterally and can cluster when ligand binds (important in receptor-mediated endocytosis).
Glycocalyx recognition — glycoproteins and glycolipids allow cells to recognise each other and distinguish "self" from "non-self" (essential in the immune system).

7. Examples of Cell Signalling in Biology

Signal	Source	Target receptor	Effect
Insulin	β-cells of pancreas	Insulin receptor on liver/muscle/fat	Glucose uptake, glycogen synthesis
Glucagon	α-cells of pancreas	Glucagon receptor on liver	Glycogen breakdown, glucose release
Adrenaline	Adrenal medulla	β-adrenergic receptor (many tissues)	Glycogenolysis, heart rate, vasoconstriction
ADH	Posterior pituitary	Kidney collecting duct cells	Insertion of aquaporins, water reabsorption
Acetylcholine	Motor neurone	Nicotinic ACh receptor on muscle	Muscle contraction
Histamine	Mast cells	H1 receptors on vessels	Vasodilation, increased permeability
FSH/LH	Anterior pituitary	Ovarian cells	Oocyte maturation, ovulation

8. Why Cell Signalling Fails — Disease Examples

Cell signalling failures cause many human diseases:

Type 2 diabetes — target cells become insensitive to insulin (receptor down-regulation and signalling defects).
Cholera — the cholera toxin permanently activates an intestinal signalling pathway, causing massive fluid loss.
Cancer — many tumours carry mutations in signalling proteins (e.g. RAS, HER2) that cause continuous "grow" signals.
Myasthenia gravis — autoantibodies block acetylcholine receptors at the neuromuscular junction, causing muscle weakness.

These examples all confirm how essential precise signalling is for normal function.

9. Common Exam Mistakes

Saying "hormones only work on cells they touch". Hormones travel in the blood to distant target cells.
Forgetting that specificity is determined by the receptor, not the hormone alone.
Confusing hormones and neurotransmitters. Hormones act over distance via blood; neurotransmitters act over tiny distances across synapses.
Writing that receptors are always intracellular. Most are membrane-bound, but steroid hormone receptors are intracellular.
Claiming that the signal itself enters the cell. Usually only the effect enters; the signal stays outside.
Omitting amplification — signalling cascades massively amplify the original signal.
Saying cells "listen" to all signals. They respond only to signals they have receptors for.

10. Exam-Style Questions

Describe the role of cell membranes in cell signalling. (4)
Explain why only target cells respond to a particular hormone. (2)
Outline how adrenaline causes an increase in blood glucose concentration. (5)
Compare hormonal and neurotransmitter signalling. (4)

Model answer for (1): "Cell membranes contain specific receptor proteins (intrinsic glycoproteins) that bind signalling molecules such as hormones and neurotransmitters. Only cells with the correct receptor respond, giving specificity. Binding of the ligand triggers a conformational change that activates an intracellular signalling cascade (e.g. production of cAMP as a second messenger), which amplifies the signal and produces a cellular response such as a change in enzyme activity or gene expression. Membranes also keep the signalling enzymes on the cytoplasmic side, separating the signalling machinery from the extracellular environment."

Summary

Cell signalling allows cells to coordinate across a multicellular organism.
The basic pathway is reception, transduction, response.
Most signals bind membrane-bound receptors, which are intrinsic glycoproteins.
Specificity comes from the match between signal and receptor; only cells with the right receptor respond.
Hormones travel in the blood and act on distant targets; neurotransmitters cross synaptic clefts.
Lipid-soluble signals (e.g. steroid hormones) cross the bilayer to bind intracellular receptors.
Signalling cascades and second messengers (such as cAMP) amplify the original signal.
Many diseases — diabetes, cholera, cancer — result from faulty signalling.

Lesson 6: Cell Signalling