Johns Hopkins scientists have uncovered new details of
how smelly things create signals in the nose that
eventually go to the brain. The findings raise issues about
how the process involved has been described for many years
in biology textbooks.
The textbooks say that our sense of smell converts
odors into brain signals just like our vision converts
light into brain signals. But the new work shows that while
a key protein pathway is used in both, it behaves quite
differently in the nose than it does in the eye. The
researchers' findings are published in the June 24 issue of
Science.
"Most of the information about this pathway comes from
studies of vision, and people just assumed it worked the
same way elsewhere in the body," King-Wai Yau, professor of
neuroscience in the Institute for Basic Biomedical
Sciences, said. "But instead of being a model for other
systems in the body, our visual system is probably pretty
unique."
At issue is the behavior 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.
Since about 1980, scientists studying vision have
understood that light activates a specific
G-protein-coupled receptor (the light-detecting molecule
rhodopsin) in cells called rods found at the back of the
eye. They also know that, once activated by light, this
particular receptor stays activated long enough to trigger
the GTP-to-GDP switch on a large number of G-protein
molecules, substantially amplifying the incoming signal.
"Because of this amplification, rods are extremely
sensitive to light," Yau said. "Each cell is capable of
signaling the absorption of a single unit, or photon, of
light."
Because G-protein signaling is so well understood in
the eye, Yau said that scientists just assumed it would
amplify signals in other systems and cells where it's
important. Indeed, some scientists have claimed that
G-protein-coupled receptors involved in detecting odors
have similar amplification abilities and that, as a result,
a single stinky molecule would produce a signal in
odor-detecting cells as large as a single unit of light
does in rods.
Trouble is, that conclusion has turned out to 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," said Vikas Bhandawat, lead author of the study
and a graduate student in neuroscience.
In his experiments, Bhandawat used a system developed
by co-author Johannes Reisert, a postdoctoral fellow, that
allows precise measurement and control of the amount of
odiferous molecules used to stimulate a single
odor-detecting nerve cell from a frog, and precise
long-term measurement of the cell's response to the
odors.
"If you don't know exactly how much of the odor is
being used, or exactly how long the exposure lasts, then
you can't figure out what a single odorant molecule does,"
Bhandawat said. "Johannes' system allows us to do just
that."
The team's finding underscores the key difference
between the eye's light-detecting system and the nose's
odor-detecting system: the very nature of light and
molecules.
"When light hits a rod and is absorbed, it's a onetime
event — the light disappears forever," Yau said. "In
the nose, an odor molecule that's inhaled probably stays in
the nasal mucus long enough to bind to and trigger a number
of receptors, essentially enhancing its own signal."
G-protein-coupled receptors are involved in thousands
of biological processes, from creating appropriate
organizational 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 behavior 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," Yau
said. "The sense of smell needs to be sensitive, but
amplification isn't the only way to improve
sensitivity."
For example, the cells could have many copies of the
receptor, or many cells could express the same receptor.
These are most likely the reasons why mice and dogs have a
heightened sense of smell compared to people, Yau said.
Authors of the paper are Bhandawat, Reisert and Yau,
all of Johns Hopkins. The research was funded by the
National Institute on Deafness and Other Communication
Disorders, the Human Frontier Science Program and the
Howard Hughes Medical Institute.
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