Lecture 7: Introduction to cell signalling Flashcards
Tuesday 21st January 2025
Signalling controls all aspects of cell behaviour, such as…
- Growth.
- Differentiation and development.
- Metabolism.
What happens if a cell does not receive signals or receives inappropriate signals? Signalling defects can have consequences for disease, such as…
cancer
heart disease
diabetes
neurological diseases, etc….
Do bacteria signal and if so, how?
- Yes
- Bacteria have membrane proteins that act as information receptors
signal -> receptor -> response
Why are small signals usually amplified?
To give a larger response
Describe the principles of signalling
- Signal: Information from beyond the plasma membrane
- Receptor: Information detector
- Amplification: Small signals are (usually) amplified within the cell to give a large response
- Response(s): Chemical changes and/or changes in gene expression
Is signal transduction a universal property of living cells?
Yes
Are signals that are produced in cells usually ligands?
Yes
What are agonists?
- Ligands that stimulate pathways.
- Most natural ligands are agonists (some are not). e.g., serotonin
What are antagonists?
- Ligands that inhibit pathways.
- Most drugs are antagonists (some are not).
e.g., antihistamines
Describe a direct contact signal and what it’s common in
- A protein (ligand) on the signalling cell binds a protein (receptor) on the target cell. The target cell responds.
- Common in tissue development. e.g., cell-to-cell contact controls eye development in Drosophila.
Describe gap jucntion signalling
- Gap junction signaling is direct cell-to-cell communication through specialized channels that allow small molecules (<1.2 kDa) and ions to pass between cells, coordinating metabolic and physiological responses.
- e.g., gap junctions are made and broken during embryo development.
- e.g., electrical synapses use gap junctions between neurons for rapid electrical transmission.
Do gap junctions involve ligands or receptors?
No. They don’t involve ligands or receptors — it’s direct cytoplasm-to-cytoplasm contact.
What do clusters of gap junctions do?
Clusters of gap junctions connect the interior of two adjacent neurons and enable the passage of electrical currents (red arrows) carried by ions as well as intracellular messengers and small metabolites.
Describe autocrine cell signalling
- the ligand induces a response only in the signalling cell.
- Most autocrine ligands are rapidly degraded in the extracellular medium. Often used to enforce developmental decisions.
- Autocrine signalling is also a common feature of cancers: auto-production of growth hormones stimulates cell proliferation.
What is the point of autocrine signalling?
Autocrine signaling helps a cell control and reinforce its own behavior — useful for rapid response, growth, feedback, and coordination in groups of similar cells.
What are Eicosanoids?
Eicosanoids are autocrine ligands derived from fatty acids and exert complex control
e.g., aggregation of platelets in the immune system, integration of pain and inflammatory responses (aspirin is an antagonist), and contraction of smooth muscle (uterus).
Describe paracrine cell signalling
- The ligand induces a response in target cells close to the signalling cell.
- This occurs when the diffusion of the ligand is limited.
- The ligand is destroyed by extracellular enzymes and internalised by adjacent cells if it doesn’t reach the target cell on time.
- e.g., paracrine signalling occurs at neuromuscular junctions.
Describe how paracrine signalling works at neuromuscular junctions
① A nerve impulse …
② … stimulates movement of synaptic vesicles, which fuse with the cell membrane …
③ … releasing acetylcholine.
④ Acetylcholine stimulates channel opening, allowing ion exchange.
⑤ The muscle twitches, and acetylcholinesterase ( ) degrades the acetylcholine.
Describe endocrince cell signalling
- the ligand is produced by endocrine cells and is carried in the blood, inducing a response in distant target cells. The ligands are often called hormones (from Gk: to set in motion).
- Human endocrine tissues include the pituitary, thyroid and adrenal glands, the pancreas, the ovaries and the testes.
Can ligands diffuse very far?
No, they can’t
Are the distinctions between different types of cell signalling always absolute? Give examples
- The distinctions are not always absolute: some ligands can belong to more than one class.
- For example, Acetylcholine as a neurotransmitter is released into a neuromuscular junction and signals in a paracrine manner: but as a hormone, it signals in an endocrine manner.
Do yeast cells respond strongly to pheromones?
No
Is cell signalling highly specific?
Yes
How many mechanisms is specificity driven by?
2
Cell-type specific expression of receptors or ligands
Loss of a component of signalling pathway that goes through the cell
+
High affinity interactions
Is differential gene expression a cell-type specificity mechanism?
Yes
Describe what differential gene expression is
Genes can be turned ‘on’ or ‘off’ by interaction of positive (activators) and negative (repressor) regulators with enhancer or silencer control elements.
What is high affinity?
Where there is a precise molecular complementarity between ligand and receptor, mediated by non-covalent forces
(like enzyme-substrate and antibody-antigen interactions)
R (receptor) + L (ligand) —> RL (receptor-ligand complex)
- Since there are two reactants, the reaction is (by definition) second order and the rate at which it occurs is determined by the concentrations of both reactants and by a constant k+
- Association rate = k+[R][L] (equation 1)
- Consider the dissociation of the receptor-ligand complex:
- RL (receptor-ligand complex) —> R (receptor) + L (ligand)
- Since there is one reactant, the reaction is (by definition) first order and the rate at which it occurs is determined by the concentrations of this reactant and by a constant k-
- Dissociation rate = k-[RL] (equation 2)
The equilibrium constant…
The equilibrium constant gives the affinity of molecules for each other and is often written Ka (association equilibrium constant). The units (per molar) are still not immediately intuitive.
…
Thus, affinity can be described in terms of concentration.
is signalling incredibly sensitive?
Yes
Describe what ‘binding’ is
- ‘Binding’ in a biochemical / physiological context is NOT just two molecules sticking together and remaining together.
- Binding is a DYNAMIC process: a mixture of association and dissociation.
What are signals typically amplified by?
enzyme cascades. These cascades can produce amplifications of several orders of magnitude within milliseconds
When does desensitisation occur?
-When a signal is present continuously, the signal transduction pathway becomes DESENSITISED.
-When the signal falls below a threshold level, the system regains sensitivity
Give an example of desensitaion
Walk from bright sunlight into a dark room: in bright sunlight your visual transduction system has become desensitised. Recovery follows as the system is re-set in the absence of continual high stimulation.
What leads to ‘cross-talk’?
Many signalling pathways share common components, leading to potential ‘cross-talk’
What is integration?
If multiple signals are given, the cell produces a unified response. The net response depends on the integrated output of both receptors
Is it true that ‘The combination of cross-talk and integration means that signal responses can be very complex’ ?
Yes
What is the difference between endocrine and exocrine glands?
Exocrine glands secrete their substances through ducts onto your body’s surfaces. On the other hand, endocrine glands secrete their substances directly into your bloodstream.
