February 07, 2003
Taste Receptor Cells Share Common Pathway
Although sweet, bitter and umami (monosodium glutamate) tastes are
different, researchers are finding that information about each of these
tastes is transmitted from the various taste receptors via a common
intracellular signaling pathway.
The identification of a common pathway runs counter to widespread
belief among some researchers in the taste field who have long held the
view that the different tastes require distinct machinery within the
cell to transduce their signals to the brain, which is responsible for
processing taste perceptions.
“We believe these findings will help us understand how tastes are encoded in the tongue and decoded by the brain.”
Charles S. Zuker
The discovery also opens the way for more precise genetic
manipulation of taste sensations in laboratory animals to discover how
different tastes are perceived in the brain, according to Howard Hughes
Medical Institute investigator Charles
Zuker, who is at the University of California, San Diego.
Zuker, Nicholas Ryba of the National Institute of Dental and
Craniofacial Research of the National Institutes of Health and their
colleagues reported their findings in the February 7, 2003, issue of
the journal Cell.
The research team reported that two enzymes found in the same
signaling pathway in the cell were necessary for mice to process sweet,
bitter and umami tastes.
According to Zuker, the effort to identify common components of the
cell machinery involved in taste was driven by two goals. “One,
is that we wanted to be able to manipulate the function of the various
taste modalities, to understand taste processing,” he said.
“We might normally seek to knock out the receptors themselves,
which is feasible with sweet receptors, since there are only a couple.
But there are thirty bitter-taste receptors, which would be practically
impossible to eliminate.
“Our other goal was to make sense of the extraordinary
complexity in the scientific understanding of the signaling pathways
involved in taste reception. We believed that it didn't make sense for
there to be multiple pathways, since all the taste receptors belonged
to only a couple of families (of proteins).”
When the researchers screened a range of taste receptor cells for
commonly expressed genes, they found two, called TRPM5 and
PLCβ2, to be widely expressed in taste cells. To
demonstrate that the two enzymes — which were known to be part of the
same signaling pathway — were necessary for taste signaling, the
researchers engineered and examined knockout mice that lacked either of
the two enzymes. These mice, they found in both electrophysiological
and behavioral tests, lacked the ability to taste sweet, bitter and
umami compounds. Also importantly, noted Zuker, the knockout mice
retained the ability to respond to salty and sour tastes.
“This told us that clearly salty and sour tastes operated
through independent mechanisms,” said Zuker. “But it also
told us that you don't need a functioning sweet, bitter or umami system
for completely normal salty and sour tastes.” In another key
experiment in the series, the researchers generated mice in which they
restored the PLCβ2 gene in only bitter taste receptors in
the PLCβ2-knockout mice. While these mice still could not
taste sweet or umami, their bitter-tasting ability was restored.
“This was a particularly important experiment that sought to
investigate another hypothesis in the taste receptor field — that
taste receptor cells are broadly tuned to all three tastes,” said
Zuker. “However, we reasoned that this didn't make sense, since
we had found a complete non-overlap in the expression of these
different receptors in taste cells. Furthermore, sweet and bitter play
very different roles in triggering behavior. The role of sweet is to
indicate a caloric food source, and bitter functions as a highly
sensitive alarm sensor for dangerous chemicals. “So this
experiment in selective rescue of these animals quite clearly showed
that restoring one modality did not restore the others, demonstrating
that taste receptor cells are not broadly tuned across all
modalities,” said Zuker.
The discovery of the common signaling molecules and the ability to
selectively knock out or rescue taste modalities provide an invaluable
tool for the next steps in understanding taste.
“We believe these findings will help us understand how tastes
are encoded in the tongue and decoded by the brain,” he said.
“We are now beginning to track the connectivity pattern from
tongue to brain. Ultimately, we hope to develop a method by which we
can visualize brain function in vivo during the animal's tasting
response.”
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