When sweet, bitter and umami molecules reach the tongue, they activate taste receptors in specialized cells called Type II taste cells. “The question that the consortium wanted to answer is, ‘how do these taste cells tell the brain that they have detected something?’ said Monell taste biologist Michael G. Tordoff, PhD. “This question has been a longstanding missing link in our understanding of taste perception.”
The scientists already knew that activation of taste receptors on Type II cells initiates a complex chain of events inside the taste cells. What they found, as reported in the current issue of Nature, is that the final step involves the opening of a pore formed by CALHM1 in the taste cell membrane. The open channel allows molecules of the neurotransmitter ATP to leave the taste cell and relay a signal to adjacent nerve cells connected to the brain.
Monell molecular neurobiologist Ichiro Matsumato, PhD, contributed to the work by showing that the gene for CALHM1 is expressed in Type II taste cells, but not in other types of taste tissue. “Our findings demonstrate that the CALHM1 pore is localized specifically in cells that detect sweet, bitter and umami taste,” said Matsumato.
The necessity of CALHM1 for the ability to taste sweet, bitter, and umami was demonstrated in behavioral tests performed by Tordoff. Reasoning that mice lacking the CALMH1 channel would not be able to release ATP to send information about sweet, bitter and umami taste detection to the brain, Tordoff tested the taste preferences of Calhm1 ‘knockout’ mice. Engineered by co-author Philippe Marambaud, PhD, of the Feinstein Institute for Medical Research, the knockout mice lack the gene that codes for CALHM1.
“Like humans, mice with an intact CALHM1 gene avidly drink sucrose and other sweeteners, and avoid bitter compounds such as quinine. However, mice lacking CALHM1 are very unusual,” said Tordoff. “These mice treat sweeteners and bitter compounds as if they were water. They behave as if they can’t taste them at all.”
Responses to salty and sour tastes were not affected by the missing gene because perception of these taste qualities is mediated via a different set of taste cells.
In combination with electrophysiological data contributed by collaborators from other institutions, the findings demonstrate that pannexins and connexins, channel proteins previously thought to be involved in ATP release from taste cells, actually are not necessary for this to happen. “This paper provides compelling data to overturn the previous hypothesis,” noted Matsumato. “It’s part of what makes science so exciting.”
Kevin Foskett, PhD, professor of Physiology at the Perelman School of Medicine, University of Pennsylvania, who with Marambaud is a senior author on the paper, recently identified CALHM1 as an ATP channel and speculated that that it might be involved in taste. “This is an example of a bona fide ATP ion channel with a clear physiological function,” said Foskett. “Now we can connect the molecular dots of sweet and other tastes to the brain.”
In addition to revealing CALHM1’s critical role in sweet, bitter, and umami taste perception, the current work also lends insight into the channel’s overall function in other tissues. Originally thought to control calcium levels inside cells, CALHM1 (calcium-homeostasis-modulator-1) may also contribute to ATP-mediated intercellular communication in the brain and elsewhere.
Additional authors include Akiyuki Taruno, Valerie Vingtdeux, Makoto Ohmoto, Zhongming Ma, Gennady Dvoryanchikov, Ang Li, Leslie Adrien, Haitian Zhao, Sze Leung, Maria Abernethy, Jeremy Koppel, Peter Davies, Mortimer M. Civan, Nirupa Chaudhari, and Goran Hellekant.
The Monell portions of this work were supported by National Institutes of Health grants DC10393, R03DC011143 and Core Grant P30DC011735.
The Monell Chemical Senses Center is an independent nonprofit basic research institute based in Philadelphia, Pennsylvania. For 45 years, Monell has advanced scientific understanding of the mechanisms and functions of taste and smell to benefit human health and well-being. Using an interdisciplinary approach, scientists collaborate in the programmatic areas of sensation and perception; neuroscience and molecular biology; environmental and occupational health; nutrition and appetite; health and well-being; development, aging and regeneration; and chemical ecology and communication. For more information about Monell, visit http://www.monell.org.