Cell Biology and Signalling Block
Signalling mechanisms Tutorial
A young doctor from the ‘Médecins sans Frontières’ organisation has been working for the
last 6 months in a rural hospital in a central Asian state. Due to political unrest in a
neighbouring country, large numbers of family groups have recently passed through the
region, camping for one or two nights by the local small river, and then moving on.
Four days after the last group had left, two local children, aged 4 and 5, were brought into
the hospital, with vomiting, and severe watery diarrhoea that had lasted several hours. Both
children were pale and exhausted to the point of collapsing. The skin was cold to the touch,
their eyes were sunken and a pulse was barely detectable.
After questioning the children and their parents, it seemed that the children had eaten
nothing different from the rest of the family, had not been in contact with the migrant group,
but they had spent one afternoon playing by the river bank.
The doctor realised the importance of treating their dehydration and electrolyte imbalance as
rapidly as possible to prevent any fatalities, and started both children on oral rehydration
therapy, giving them drinks made from sugar and salt from the hospital store.
A sample of the watery diarrhoea fluid was obtained from one child and showed the
presence of a few gram-negative bacteria, each with a single flagellum, probably Vibrio
cholerae.
Questions
1. What disease does the doctor suspect is causing the symptoms of vomiting
and diarrhoea in these children?
Cholera
2. What is the probable route by which the children picked up this infection?
Transmission via the river (water is the vector)
3. Many intestinal bacteria that cause disease do so by producing toxins, which
interfere with membrane signalling pathways. With a remarkable feat of
memory, the doctor remembered from his college textbooks that Vibrio
cholerae produces a toxin, which enters epithelial cells and causes irreversible
modification of the Gs protein, ultimately leading to increased ion and water
transport across the gut wall into the lumen. Gs proteins are part of a system
involved in the transmission of extracellular signals to intracellular responses.
Draw a diagram and identify as many features of one such signalling system as
you can
4. Explain what is meant by the term ‘second messenger’.
5. Give two other examples of second messengers other than cAMP.
6. Describe the structure, biochemical properties and functional role of a typical Gs protein.
7. In the presence of the cholera toxin, the modified -subunit of the G-protein loses its
GTPase activity. What type of biomolecule is the toxin likely to be if it has a molecular mass
of 87,000 and catalyses the covalent modification of the G-protein?
8. How are signalling mechanisms involving second messengers such as cAMP switched off?
9. In gut epithelial cells, raised levels of cAMP activate a cascade process, via a cAMP
dependent protein kinase, that eventually leads to the phosphorylation of a transport
- + -
protein which controls the secretion of a Cl , Na and HCO3 -rich digestive fluid into the
lumen of the gut. What would be the biochemical consequences of the adenylate cyclase
being permanently activated?
10. The urgent aspect of treatment of a patient with cholera is to replace the huge volume of
water and salts lost through diarrhoea. Oral rehydration treatment involves drinking a
+
solution made with glucose and salt. Explain how this would maintain Na transport into the
+
cell (with water following the Na ions)
11. As cholera is a disease of developing countries, explain why oral rehydration therapy is
preferable to vaccination programmes, treatment with antibiotics, or intravenous
rehydration with glucose and saline solutions.
12. cAMP acts as the second messenger for several polypeptide hormone / receptor signalling
systems. What might be the physiological consequences of raised intracellular levels of
cAMP in liver in response to the binding of the hormone glucagon to the liver glucagon-
specific receptor?
