Smell, intimately related to how human beings taste food, has long remained the most enigmatic of our senses.
The average human nose can detect nearly 10,000 distinct scents, a feat that requires about 1,000 olfactory genes, or roughly 3 per cent of the human genome.
While previous science has suggested that our sense of smell converts odours into brain signals just like our vision converts light into brain signals.
New work from researchers at the Johns Hopkins Medical Institution in the US shows that while a key protein pathway is used in both, it behaves quite differently in the nose than it does in the eye.
At issue is the behaviour of a huge family of proteins called G-protein-coupled receptors. When activated by light in the eye or a molecule in other settings, each G-protein-coupled receptor uses a similar switch - the exchange of a tiny bit called GTP for a related bit called GDP on the aptly named G-protein - to trigger the cell's response.
Because G-protein signaling is so well understood in the eye, King-Wai Yau, professor of neuroscience in Johns Hopkins' Institute for Basic Biomedical Sciences says scientists just assumed that it would amplify signals in other systems and cells where it is important.
Some scientists have claimed that G-protein-coupled receptors involved in detecting odours have similar amplification abilities and that, as a result, a single smelly molecule would produce a signal in odour-detecting cells as large as a single unit of light does in rods.
But the conclusion may be wrong.
"We found that most of the time, a single molecule does not trigger a response. And even when it does, the response we measured is about 100 times lower than reported for rods [in eyes]," says Vikas Bhandawat, lead author of the study.
Bhandawat used a system developed by co-author Johannes Reisert that allows precise measurement and control of the amount of odiferous molecules used to stimulate a single odour-detecting nerve cell from a frog, and precise, long-term measurement of the cell's response to the smells.
"If you don't know exactly how much of the odour is being used, or exactly how long the exposure lasts, then you can't figure out what a single odorant molecule does," says Bhandawat.
In the nose, an odour molecule that is inhaled probably stays in the nasal mucus long enough to bind to and trigger a number of receptors, essentially enhancing its own signal.
According to the researchers, G-protein-coupled receptors are involved in thousands of biological processes, from creating appropriate organisational cues during development to transmitting signals from hormones and other molecules in fully grown adults, and are present in creatures from the amoeba to plants and animals.
"We think the mode of receptor behaviouur in odor detection is more the norm for chemical-triggered G-protein pathways, which are by far the most common G-protein signaling pathways, than is what happens in the eye," says Yau.
Last year Richard Axel and Linda Buck were awarded a joint Nobel Prize in Physiology or Medicine for their pioneering research on this mysterious sense.
The two scientists had jointly published a fundamental paper in which they described the large family of 1,000 olfactory genes, clarifying for the first time how our olfactory system works.