Double defense against self-recognition

When erroneous production occurs, yeast cells can prevent responding to their own signals

To the Point

• Unreliable principle: Yeast cells recognize each other through different sex pheromones and specific receptors. Accidental production of the “foreign receptor” could cause cells to respond to their own signals.
• Unknown corrective mechanism: This mechanism provides additional protection against self-recognition.
• Universal principle in eukaryotes: The mechanism helps prevent autocrine signaling. This is relevant for immune responses and growth signals, where a failure in control can have serious consequences.

In other organisms, the sexes are referred to as 'male' and 'female'; in yeast cells, however, we speak of 'mating types'. How do yeast cells recognise the other type? In other words: How do they distinguish 'self' from 'non-self'? The principle is simple: the two partners secrete different sex pheromones and have receptors on their cell surfaces that bind exclusively to the pheromone of the other mating type.

Although both mating types possess the genetic blueprints for both the pheromone and the receptor, a cell should only produce its own receptor. This regulation usually occurs at a genetic level, for instance by suppressing gene expression. Under normal conditions, the activity of the 'foreign' receptor is undetectable and the cells do not respond to their own pheromone.

Self-produced foreign receptor

The team led by Victor Sourjik made a surprising discovery: when pheromone production was suppressed, the activity of the foreign receptor in the cell became detectable. Apparently, the receptor, which normally only occurs in the mating partner, was being produced in small quantities by the cell itself. How does the yeast cell prevent a reaction to its own pheromone despite this misproduction? 'A reaction to its own signals would not only impair mating, but also reduce fitness,' explains Alexander Anders.

Upon closer examination, the team discovered a previously unknown protective mechanism: the cell's own pheromone binds to the foreign receptor inside the cell and eliminates it before it can reach the cell surface. Only the correct receptors, which recognise the signals of the other mating type, reach the surface. 'The fact that a receptor is intercepted inside the cell by its own signal shows that cells exercise control much earlier and more precisely than previously assumed,' the microbiologist explains. 'The principle resembles the training of T cells in the immune system during cell maturation — here, too, the cell must learn to react only to foreign cells and molecules, and not to its own.'

The interception mechanism - an universal principle?

The research team suspects that this form of 'proofreading' plays a fundamental role in the biological world of eukaryotes, from microbial yeasts to humans.
'This discovery shows not only how yeast cells ensure their mating type recognition. It could also be a universal strategy to prevent autocrine signalling, i.e. the response to self-produced signals,” adds Victor Sourjik. Understanding these processes could also be relevant for regulating immune responses or growth signals, as failure of the control mechanisms can have serious consequences in these contexts.