Lecture 7: Introduction to cell signalling

Question 1

Signalling controls all aspects of cell behaviour, such as…

Answer 1

• Growth.
• Differentiation and development.
• Metabolism.

Question 2

What happens if a cell does not receive signals or receives inappropriate signals? Signalling defects can have consequences for disease, such as…

Answer 2

• cancer
• heart disease
• diabetes
• neurological diseases, etc….

Question 3

Do bacteria signal and if so, how?

Answer 3

• Yes
• Bacteria have membrane proteins that act as information receptors

signal -> receptor -> response

Question 4

Why are small signals usually amplified?

Answer 4

To give a larger response

Question 5

Describe the principles of signalling

Answer 5

• 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

Question 6

Is signal transduction a universal property of living cells?

Answer 6

Yes

Question 7

Are signals that are produced in cells usually ligands?

Answer 7

Yes

Question 8

What are agonists?

Answer 8

• Ligands that stimulate pathways.
• Most natural ligands are agonists (some are not). e.g., serotonin

Question 9

What are antagonists?

Answer 9

• Ligands that inhibit pathways.
• Most drugs are antagonists (some are not).
  e.g., antihistamines

Question 10

Describe a direct contact signal and what it’s common in

Answer 10

• 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.

Question 11

Describe gap jucntion signalling

Answer 11

• 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.

Question 12

Do gap junctions involve ligands or receptors?

Answer 12

No. They don’t involve ligands or receptors — it’s direct cytoplasm-to-cytoplasm contact.

Question 13

What do clusters of gap junctions do?

Answer 13

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.

Question 14

Describe autocrine cell signalling

Answer 14

• 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.

Question 15

What is the point of autocrine signalling?

Answer 15

Autocrine signaling helps a cell control and reinforce its own behavior — useful for rapid response, growth, feedback, and coordination in groups of similar cells.

Question 16

What are Eicosanoids?

Answer 16

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).

Question 17

Describe paracrine cell signalling

Answer 17

• 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.

Question 18

Describe how paracrine signalling works at neuromuscular junctions

Answer 18

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.

Question 19

Describe endocrince cell signalling

Answer 19

• 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.

Question 20

Can ligands diffuse very far?

Answer 20

No, they can’t

Question 21

Are the distinctions between different types of cell signalling always absolute? Give examples

Answer 21

• 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.

Question 22

Do yeast cells respond strongly to pheromones?

Answer 22

Yes

Question 23

Is cell signalling highly specific?

Answer 23

Yes

Question 24

How many mechanisms is specificity driven by?

Answer 24

2

Cell-type specific expression of receptors or ligands

Loss of a component of signalling pathway that goes through the cell

+

High affinity interactions

Question 25

Is differential gene expression a cell-type specificity mechanism?

Answer 25

Yes

Question 26

Describe what differential gene expression is

Answer 26

Genes can be turned ‘on’ or ‘off’ by interaction of positive (activators) and negative (repressor) regulators with enhancer or silencer control elements.

Question 27

What is high affinity?

Answer 27

Where there is a precise molecular complementarity between ligand and receptor, mediated by non-covalent forces (like enzyme-substrate and antibody-antigen interactions)

Question 28

R (receptor) + L (ligand) ---> RL (receptor-ligand complex)

Answer 28

- 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)

Question 29

The equilibrium constant...

Answer 29

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.

Question 30

is signalling incredibly sensitive?

Answer 30

Yes

Question 31

Describe what 'binding' is

Answer 31

- ‘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.

Question 32

What are signals typically amplified by?

Answer 32

enzyme cascades. These cascades can produce amplifications of several orders of magnitude within milliseconds

Question 33

When does desensitisation occur?

Answer 33

-When a signal is present continuously, the signal transduction pathway becomes DESENSITISED. -When the signal falls below a threshold level, the system regains sensitivity

Question 34

Give an example of desensitaion

Answer 34

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.

Question 35

What leads to 'cross-talk'?

Answer 35

Many signalling pathways share common components, leading to potential ‘cross-talk’

Question 36

What is integration?

Answer 36

- If multiple signals are given, the cell produces a unified response. - The net response depends on the integrated output of both receptors

Question 37

Is it true that 'The combination of cross-talk and integration means that signal responses can be very complex' ?

Answer 37

Yes

Question 38

What is the difference between endocrine and exocrine glands?

Answer 38

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.