Sense of Smell Wins Nobel Prize
Medical Authors and Editors:
Barbara K. Hecht,
Ph.D. and
Frederick Hecht, M.D.
Oct 4, 2004 -- Two American investigators Richard Axel
and Linda B. Buck have received the 2004 Nobel Prize in Physiology or Medicine for their work
on "odorant receptors and the organization of the olfactory system" -- the sense of smell.
In 1991 Axel and Buck jointly discovered a very large
family of about one
thousand genes for odorant receptors. They have since worked independently
and have in elegant, often parallel, studies they have clarified the
olfactory system from the molecular level to the organization of the cells.
Dr. Axel is at the Howard Hughes Medical Institute and Columbia University in New York, while Dr. Buck is at
the Fred Hutchinson Cancer Research Center in Seattle. The Sense of Smell
The sense of smell has long remained the most enigmatic of our senses.
The basic principles for recognizing and remembering about 10,000 different
odors have not been understood. Drs. Axel and Buck have "solved this problem
and in a series of pioneering studies clarified how our olfactory system
works," according to the Nobel Assembly at the Karolinska Institute in
Stockholm.
The Gene Family
The gene family that Axel and Buck discovered contains 1,000 or so genes. It
is truly a superfamily of genes, accounting for about 3% of all human genes.
The olfactory genes in this superfamily gives rise to an equivalent number
of olfactory receptor types. These receptors are located on specialized
cells called olfactory receptor cells, which occupy a small area in the
upper part within the nose and detect the inhaled odorant molecules.
Each olfactory receptor cell possesses only one type of odorant receptor,
and each receptor can detect a limited number of odorant substances. Our
olfactory receptor cells are therefore highly specialized for a few odors.
Smell Cells
The olfactory receptor cells send thin nerve processes directly to distinct
microdomains, called glomeruli, in the olfactory bulb.
The olfactory bulb is the primary area of the brain for olfaction. Receptor cells carrying the
same type of receptor send their nerve processes to the same glomerulus.
From these microdomains in the olfactory bulb, the information is relayed
further to other parts of the brain, where the information from several
olfactory receptors is combined, forming a pattern.
Lilacs and Strawberries
Thanks to this olfactory system, we can consciously experience the smell of
a lilac flower in the spring and recall this olfactory memory at other
times, noted the Nobel Assembly.
When something tastes really good it is primarily activation of the
olfactory system which helps us detect the qualities we regard as positive.
A good wine or a sunripe wild strawberry activates a whole array of odorant
receptors, helping us to perceive the different odorant molecules.
Loss of Sense of Smell
A unique odor can trigger distinct memories from our childhood or from emotional moments
later in life. A single clam that is not fresh and makes us sick can leave a
memory that stays with us for years, and prevents us from ingesting any dish, however delicious, with clams in it.
To lose the sense of smell is a serious handicap -- we no
longer perceive the different qualities of food and we cannot detect warning signals, for
example smoke from a fire.
The following sections provide more information about the
science of our
system of smell and are based upon the press release today from the Nobel
Assembly.
Deciphering a Sensory
System
The olfactory system
is the first of our sensory systems that has been deciphered primarily using
molecular techniques. Axel and Buck showed that 3% of our genes are used to code
for the different odorant receptors on the
membrane of the olfactory receptor cells. When an odorant receptor is
activated by an odorous substance, an electric signal is triggered in the
olfactory receptor cell and sent to the brain via nerve processes.
Each odorant receptor first activates a G protein, to which it is coupled.
The G protein in turn stimulates the formation of cAMP (cyclic
AMP). This messenger molecule activates ion channels, which are opened and
the cell is activated. Axel and Buck showed that the large family of odorant
receptors belongs to the G protein-coupled receptors (GPCR).
All the odorant receptors are related proteins but differ in certain
details, explaining why they are triggered by different odorous molecules.
Each receptor consists of a chain of amino acids that is anchored into the
cell membrane and traverses it seven times. The chain creates a binding
pocket where the odorant can attach. When that happens, the shape of the
receptor protein is altered, leading to G protein activation.
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