The Secret Functioning of Odor Receptors, Finally Revealed

The team’s observations may explain how insect olfactory receptors can generally evolve so rapidly and diverge so much between species. Each species of insect may have evolved “its unique repertoire of receptors that are really well adapted to its particular chemical niche,” Ruta said.

“It tells us that it goes beyond just the idea that receptors interact freely with a mass of ligands,” Datta said. A receptor built around a single binding sac, with a response profile that can be retrieved from the smallest of clusters, could accelerate evolution by freeing it to explore a wide spectrum of chemical repertoires.

The receiver architecture also supported this view. Ruta and her colleagues found that it consisted of four subunits of proteins bound freely to the central pore of the canal, like the petals of a flower. Only the central region needed to be preserved as the diversified and evolved receptor; the genetic sequences that govern the rest of the receptor unit were less constrained. This structural organization meant that the receptor could accommodate a wide degree of diversification.

Such mild evolutionary restrictions at the receptor level probably impose a substantial selective pressure downstream of the neural circuits for olfactory: the nervous systems need good mechanisms to decode the disordered patterns of receptor activity. “Indeed, olfactory systems have evolved to take arbitrary patterns of receptor activation and give them meaning through learning and experience,” Ruta said.

Interestingly, however, nervous systems do not seem to make the problem easier for themselves. The scientists had widely assumed that all the receptors of an individual olfactory neuron were of the same class, and that neurons for different classes went into segregated transformation regions of the brain. In a pair of preprints sent last November, however, the researchers reported that in flies and mosquitoes, individual olfactory neurons express more classes of receptors. “That’s really amazing, and it would further increase the diversity of sensory perception,” Barber said.

The results of the Route team are far from the last word on the functioning of olfactory receptors. Insects use many other classes of olfactory receptors of ion channels, including those that are much more complex and much more specific than those in the saliva. In mammals, the olfactory receptor is not even an ion channel; belongs to an entirely different family of proteins.

“This is the first odor recognition structure in every receptor by any species. But it’s probably not the only odor recognition mechanism,” Ruta said. “That’s just one solution to the problem. It would be very unlikely to be the only solution.”

Even so, she and other researchers think there are many more general lessons to be learned from the living room olfactory receptor. It is tempting, for example, to imagine how this mechanism could apply to other receptors in the animal’s brain – from those that detect neuromodulators such as dopamine to those affected by various types of anesthetics – “and how inaccurate they are.” allowed “to be,” Barber said. “It offers a fascinating model for continuing to explore nonspecific link interactions.”

Perhaps this flexible-binding approach should be considered in other contexts as well, he added. Published research in the Proceedings of the National Academy of Sciences March, for example, suggested that even the canonical lock and key receptors of ion channels might not be as strictly selective as scientists thought.

If several different types of proteins bind to receptors through flexible and weak interactions in some type of task, that principle could guide the rational conception of drugs for various diseases, particularly neurological conditions. At a minimum, Ruta’s work on the link of DEET to an olfactory insect receptor could provide insights into how to develop targeted repellents. “The mosquito is still the deadliest animal on Earth” because of the diseases it carries, Ruta said.