In their hunt for genes and proteins that explain how
animals discern bitter from sweet, a team of Johns Hopkins
researchers began by testing whether mutant fruit flies
prefer eating sugar over sugar laced with caffeine. Using a
simple behavioral test, the researchers discovered that a
single protein missing from the fly-equivalent of human
taste buds caused them to ignore caffeine's taste and
consume the caffeine as if it were not there.
"No, you won't see jittery Drosophila flitting past
your bananas to slurp your morning java anytime soon," said
Montell, a professor of
chemistry in the
Institute of Basic Biomedical Sciences at Johns
Hopkins. "The bottom line is that our mutant flies
willingly drink caffeine-laced liquids and foods because
they can't taste its bitterness — their taste
receptor cells don't detect it."
The Johns Hopkins flies, genetically mutated to lack a
certain taste receptor protein, have been the focus of
studies to sort out how animals taste and why humans like
the taste of some things but are turned off by the taste of
By color-coding sweet and bitter substances eaten by
fruit flies and examining the coloring that showed up in
their translucent bellies, the Johns Hopkins team hoped to
learn whether flies missing a specific "taste-receptor"
protein changed their taste preferences.
"Normally," Montell said, "when given the choice
between sweet and bitter substances, flies avoid caffeine
and other bitter-tasting chemicals. But flies missing this
particular taste-receptor protein, called Gr66a, consume
caffeine because their taste-receptor cells don't fire in
response to it."
The discovery, which is the first-ever example of a
protein required for both caffeine tasting and
caffeine-induced behav-ior, was published Sept. 19 in
For the study, Montell and his colleagues kept 50
fruit flies away from food overnight and for breakfast gave
the starved flies 90 minutes to eat as much as they wanted
of either or both of two concoctions: a blue-colored
mixture of sugar and agar and a red-colored mixture of
caffeine, sugar and agar. The researchers then flipped the
flies onto their backs and looked at the color of their
bellies to see what they ate — blue indicating a
preference for eating sugar, red indicating a preference
for bitter caffeine and purple indicating no preference.
Flies missing the critical taste receptor protein
Gr66a consumed the bitter caffeine solution to the same
extent as the sugar-only solution. Montell and colleagues
conclude that Gr66a is crucial for the normal caffeine
avoidance behavior and, without it, flies are seemingly
indifferent to the bitter taste.
The researchers went on to examine whether this
indifference to bitter was due to the taste nerves on the
fly's "tongue" or some malfunction in the fly's brain.
Chemical stimulants trigger taste receptor cells to send an
electrical current to the brain where the information is
processed and often leads to a change in behavior, such as
the decision to eat or avoid.
With fine tools, the research team recorded electrical
currents in those cells known to contain the Gr66a caffeine
taste receptor in the fly's equivalent of the taste buds,
dubbed the taste bristles.
Applying sugar to the taste bristles of normal flies,
or to mutant flies missing the Gr66a protein, caused the
neurons to produce electrical current "spikes" at a
frequency of about 20 spikes per second. Other bitter
compounds such as quinine generated electrical current
spikes at about the same frequency in the mutants.
Only flies missing the Gr66a taste receptor protein
were unable to generate any current spikes when given
caffeine. "This is a clear demonstration that Gr66a is
functioning in the taste receptor cells and is not a
'general sensor' for bitter compounds but is required more
specifically for the caffeine response," Montell said.
"This indicates that flies have different receptors for the
response to other types of bitter compounds.
"We also tested whether the flies avoided the related
bitter compounds found in tea and cocoa — chocolate
— and found that Gr66a also is required for the
response to the compound in tea but not for the one in
chocolate," he said.
Fruit flies often are used as experimental organisms
because they grow quickly and are easy to manipulate
genetically. Now that Montell and his colleagues have a
mutant fly that is unable to taste caffeine, they hope to
further examine the other genes and molecules involved in
the caffeine response and better understand the
biochemistry behind caffeine-induced behavior in other
organisms, namely humans.
The researchers were funded by the Polycystic Kidney
Disease Foundation and the National Institute of Deafness
and Communicative Disorders of the National Institutes of
Authors on this paper are Seok Jun Moon, Michael
Kottgen, Yuchen Jiao, Hong Xu and Montell, all of Johns