Monell Center Researchers, Collaborators ID Critical Olfactory Protein

Researchers at the Monell Center and collaborators have identified a protein that is critical to the ability of mammals to smell, which may provide insight into the underlying causes of certain smell disorders in humans.

According to a study published in the Journal of Neuroscience, "Without G γ13, the mice cannot smell," said senior author Liquan Huang, a molecular biologist at Monell. "This raises the possibility that mutations in the G γ13 gene may contribute to certain forms of human anosmia [the inability to smell] and that gene sequencing may be able to predict some instances of smell loss."

Odor molecules entering the nose are sensed by a family of olfactory receptors. Inside the receptor cells, a complex cascade of molecular interactions converts information to ultimately generate an electrical signal. This signal, called an action potential, is what tells the brain that an odor has been detected. To date, the identities of some of the intracellular molecules that convert odor information into an action potential remain a mystery, researchers said. Suspecting that a protein called G γ13 might be involved, the research team engineered mice to be lacking this protein and then tested how the 'knockout' mice responded to odors.

Because the G γ13 protein plays critical roles in other parts of the body, the G γ13 'knockout' was confined exclusively to smell receptor cells. This specificity allowed the researchers to characterize the effect of G γ13 deletion on the olfactory system without interference from changes in other tissues. Both behavioral and physiological experiments revealed that the G γ13 knockout mice did not respond to odors.

In behavioral tests, control mice with an intact sense of smell were able to detect and retrieve a piece of buried food in less than 30 seconds. However, mice lacking G γ13 in their olfactory cells required more than eight minutes to perform the same task. Both sets of mice were able to quickly locate the food when it was placed in plain sight.

A second set of experiments measured olfactory function on a physiological level. Using olfactory tissue from knockout and control mice, the researchers recorded electrical responses to 15 different odors. Responses from the G γ13 knockout mice were greatly reduced, suggesting that the olfactory receptors of these mice were unable to translate odor signals into an electrical response.

Together, researchers said the findings demonstrate that G γ13 is essential for mammals to smell odors and extend the current understanding of how olfactory receptor cells communicate information about odors to the brain. Future studies will seek to identify how G γ13 interacts with other molecules within the olfactory receptor.

"Loss of olfactory function can greatly reduce quality of life," said Huang. "Our findings demonstrate the significant consequences when just one molecular component of this complex system does not function properly."

More in Regulatory & Research