EMBL study improves understanding of how hormones work

When studying protein complexes in yeast, scientists at the European Molecular Biology Laboratory (EMBL) gained new insight into a crucial signalling process also found in humans: signal chains
similar to pheromone signals stimulating mating in yeast are involved in the differentiation of human nerve cells and the development of cancer.

When a nearby yeast cell releases a pheromone – inducing mating behaviour -the pheromone docks on to a receptor on another cell’s exterior and triggers a signalling chain on the inside of the
cell. A series of proteins called MAP kinases pass on the signal, eventually initiating the formation of the mating organ and the fusion of the cells.

The scientists used fluorescent molecules to mark the MAP kinase signalling chain. ‘Our method is so precise that we could virtually count the molecules and the interactions between chain
components,’ says researcher Michael Knop. ‘To our surprise, the observed proteins in the cell’s interior did not interact more after stimulation by the pheromone. This means changes in
interaction are not the way by which the signal is transmitted through the interior of the cell.’

Instead of the signal spreading uniformly throughout the cell, observation showed that it is only produced in the chain components found in the mating organ. The components, however, activate a
protein called Fus3, which diffuses into the centre of the cell. On its way, Fus3 is constantly deactivated by other proteins.

‘We found that the concentration of Fus3 activity is very high at the tip of the developing mating organ and then gradually gets less towards the centre of the cell,’ says Celine Maeder, who
carried out the research in Dr Knop’s lab. ‘This sets up a gradient of Fus3 activity, which might allow the signal to have different effects in different parts of the cell.’

‘This result is exciting,’ concludes former EMBL group leader Philippe Bastiaens. ‘It revolutionises our understanding of signalling processes and the way we need to study them.’ As the MAP
kinase signalling chain is conserved across species, the findings of the yeast study improve understanding of a pathway that also plays a role in human biology and disease.