Cells communicate by sending and receiving chemical signals called ligands. A signal molecule binds to a receptor (on the membrane surface or inside the cell), triggering a transduction cascade that amplifies the message and produces a cellular response. The three main types of membrane receptors are G protein-coupled receptors, receptor tyrosine kinases, and ion channel receptors.
Difficulty: Introductory to Intermediate | Prerequisites: Membrane structure and transport (Doc 1), basic protein structure.
No cell works in isolation. In a multicellular organism, coordinated behaviour depends on cells sending and receiving signals, from the growth factors that tell a wound to heal to the neurotransmitters that let you read this sentence. This topic builds directly on membrane structure: most receptors are transmembrane proteins, and many signals never cross the membrane at all. You should be comfortable with membrane proteins, ATP, and phosphorylation before working through this material. If you are not, review the membrane and energy notes first.
Ligand
A molecule or ion that binds to a receptor to initiate a signalling sequence. Local regulators, neurotransmitters, and hormones are all ligands.
Think of it as the "key" that fits into a receptor's "lock."
Receptor
The target site where a ligand binds, causing a conformational change that triggers a cellular response.
Target cell
The specific cell that contains a receptor for a particular ligand and therefore responds to that signal.
G protein-coupled receptor (GPCR)
The largest family of cell-surface receptors. GPCRs interact with G proteins, which toggle between an active state (bound to GTP) and an inactive state (bound to GDP).
Receptor tyrosine kinase (RTK)
A membrane receptor that, when activated, phosphorylates tyrosine residues on proteins using phosphate groups from ATP.
Ion channel receptor (ligand-gated ion channel)
A membrane receptor that opens or closes an ion channel in response to ligand binding, allowing ions to flow across the membrane.
Kinase
An enzyme that transfers phosphate groups from ATP to a substrate, phosphorylating it and changing its activity.
In simple terms, a kinase is an "on switch" that adds a phosphate tag to activate or deactivate a protein.
Phosphatase
An enzyme that removes phosphate groups from proteins, reversing the action of kinases.
Second messenger
A small intracellular molecule (such as cAMP or Ca2+) that relays and amplifies the signal from the receptor to target molecules inside the cell.
Adenylyl cyclase
An enzyme that converts ATP to cyclic AMP (cAMP), a common second messenger.
Phosphodiesterase
An enzyme that breaks down cAMP, ending its signalling role.
Transcription factor
A protein that binds to DNA and regulates gene expression. Some intracellular receptors act as transcription factors when activated by a ligand.
Paracrine signalling
Signalling between nearby cells, where the signal molecule (e.g. a growth factor) travels only a short distance.
Synaptic signalling
A specialised form of paracrine signalling between two cells connected by a synapse, using neurotransmitters.
Autocrine signalling
Signalling in which a cell releases a ligand that binds to receptors on its own surface.
Exocrine / hormonal signalling (long-distance signalling)
Signalling via hormones released into the bloodstream, reaching target cells far from the source.
Signal transduction
The process by which an extracellular signal is converted into a specific intracellular response, typically through a cascade of molecular interactions.
Multicellular organisms have two broad strategies for cell-to-cell communication:
Direct contact: cells physically touch, allowing signals to pass through gap junctions or surface molecules
Indirect messaging: a cell releases a signalling molecule (a ligand) that travels to a target cell
Paracrine signalling: the ligand acts on nearby cells (e.g. growth factors during wound healing)
Synaptic signalling: a neurotransmitter crosses a synapse to reach the adjacent neuron or muscle cell
Autocrine signalling: the cell's own ligand binds back to receptors on its own surface
Exocrine / hormonal signalling: a hormone is released into the bloodstream and travels to distant target cells throughout the body
In the plasma membrane: most water-soluble signal molecules bind to receptor proteins that span the membrane
In the cytoplasm or nucleus (intracellular receptors): small or hydrophobic signal molecules (e.g. steroid hormones) can cross the membrane and bind to receptors inside the cell, where the activated hormone-receptor complex may act directly as a transcription factor
1. G Protein-Coupled Receptors (GPCRs)
The largest family of cell-surface receptors
When a ligand binds, the receptor activates a G protein on the cytoplasmic side
G proteins toggle between an active state (bound to GTP) and an inactive state (bound to GDP)
The activated G protein triggers downstream enzymes or ion channels
Many GPCRs activate adenylyl cyclase, which converts ATP to the second messenger cAMP
2. Receptor Tyrosine Kinases (RTKs)
A kinase is an enzyme that transfers a phosphate group from ATP to a protein (phosphorylation)
RTKs phosphorylate tyrosine residues on target proteins, activating multiple signalling pathways at once
Important in growth factor signalling
3. Ion Channel Receptors (Ligand-Gated Ion Channels)
A ligand binds and the channel opens, allowing specific ions to flow across the membrane
Particularly important in neuron function
A signal arriving at the membrane is relayed through a series of intracellular molecules before producing a response
Each step in the cascade is an opportunity for regulation and coordination
Multistep pathways amplify the signal: a few ligand molecules at the surface can produce a large cellular response
Second messengers (cAMP, calcium ions Ca2+) spread the signal rapidly within the cell
Some signalling pathways end at the nucleus, where they activate or inhibit transcription factors
Transcription factors are proteins that bind to DNA and control which genes are expressed
The result is a controlled increase or decrease in the production of particular proteins
Four essentials for understanding how neurons signal:
Resting potential: the membrane potential of a neuron at rest is approximately -70 mV, maintained by ion channels that allow K+ and Na+ to leak at different rates
The inside of the cell has more K+ (making it more negative); the outside has more Na+ (more positive)
Sodium-potassium pump: an active transport pump (requires ATP) that moves 3 Na+ out and 2 K+ in, maintaining the resting potential and the electrochemical gradient
Voltage-gated ion channels: these channels respond to changes in membrane potential; when the membrane depolarises past a threshold, voltage-gated Na+ channels open, triggering an action potential
Action potential: a rapid depolarisation that propagates along the axon; initiated at the axon hillock, each action potential triggers the next segment of the axon to depolarise
Ions can have a depolarising effect (making the membrane less negative, moving toward firing) or a hyperpolarising effect (making it more negative, moving away from firing).
Students often think all signals must enter the cell to have an effect. Most water-soluble ligands never cross the membrane; they bind to surface receptors and trigger intracellular cascades.
Students confuse kinases and phosphatases. Kinases add phosphate groups (from ATP); phosphatases remove them. They are opposing switches.
Students sometimes think signal amplification means the signal gets "louder" at each step. What it means is that one activated receptor can activate many downstream molecules, so the number of responding molecules increases at each stage.
Students mix up depolarisation and hyperpolarisation. Depolarisation makes the membrane potential less negative (closer to firing); hyperpolarisation makes it more negative (further from firing).
⚠️ Know the three types of membrane receptors (GPCRs, RTKs, ion channel receptors) and what distinguishes each.
⚠️ Understand the G protein cycle: inactive (GDP-bound) to active (GTP-bound) and back.
⚠️ Be able to explain signal amplification and why multistep cascades are advantageous.
⚠️ Know the difference between local signalling (paracrine, synaptic, autocrine) and long-distance signalling (hormonal/exocrine).
⚠️ Understand the four key concepts for neuron signalling: resting potential, sodium-potassium pump, voltage-gated ion channels, action potential.
True or False: G proteins are active when bound to GDP. (False: they are active when bound to GTP and inactive when bound to GDP.)
Fill in the blank: A ___ is an enzyme that adds phosphate groups to proteins. (kinase)
True or False: Steroid hormones typically bind to receptors on the cell surface. (False: they are hydrophobic and cross the membrane to bind intracellular receptors.)
Fill in the blank: The resting potential of a neuron is approximately ___ mV. (-70)
True or False: In synaptic signalling, the signal molecule travels through the bloodstream. (False: it crosses a synapse between two adjacent cells. Bloodstream transport is hormonal/exocrine signalling.)
Q: What is the difference between paracrine and exocrine (hormonal) signalling?
A: In paracrine signalling, the ligand acts on nearby cells over a short distance. In exocrine/hormonal signalling, the ligand (a hormone) enters the bloodstream and travels to target cells in distant parts of the body.
Q: Explain how a G protein-coupled receptor activates a cellular response.
A: A ligand binds the GPCR, which changes shape and activates an associated G protein by causing it to release GDP and bind GTP. The active G protein then activates a downstream enzyme (e.g. adenylyl cyclase), which produces a second messenger (e.g. cAMP) that relays the signal further into the cell.
Q: Why are multistep signal transduction pathways advantageous?
A: Each step provides an opportunity for regulation, coordination, and amplification. A single ligand-receptor interaction at the surface can activate many molecules at each stage, producing a large cellular response from a small initial signal.
Q: What role do calcium ions play in cell signalling?
A: Calcium ions (Ca2+) are common second messengers. When released from intracellular stores (such as the endoplasmic reticulum), they activate a variety of proteins and enzymes that carry out the cellular response.
Q: Describe the sequence of events that produces an action potential in a neuron.
A: At rest, the neuron membrane sits at about -70 mV, maintained by ion channels and the sodium-potassium pump. When a stimulus depolarises the membrane past the threshold at the axon hillock, voltage-gated Na+ channels open, Na+ rushes in, and the membrane potential rises sharply (depolarisation). This depolarisation triggers adjacent voltage-gated channels to open, propagating the action potential along the axon.
Cell communication relies on the membrane proteins and transport mechanisms covered in Doc 1 (Biological Membranes). Receptor proteins are transmembrane proteins; the ion gradients that power neuron signalling are maintained by the sodium-potassium pump.
The energy required for phosphorylation cascades and active transport ties directly to thermodynamics and enzymes (Doc 3). Understanding ATP hydrolysis as an exergonic reaction explains where the energy for kinase activity and pump operation comes from.
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