Investigators Figure Out How We Taste Sweetness and Bitterness

A team of investigators from nine institutions has shed light on how cells transmit taste information to the brain for three out of the five primary taste types, sweet, bitter, and umami. They have discovered how ATP - the body's main fuel source- is released as the neurotransmitter from sweet, bitter, and umami, or savory, taste bud cells.

The CALHM1 channel protein, which spans a taste bud cell's outer membrane to allow ions and molecules in and out, releases ATP to make a neural taste connection. The other two taste types, sour and salt, use different mechanisms to send taste information to the brain.

Kevin Foskett, PhD, professor of Physiology at the Perelman School of Medicine, University of Pennsylvania, and colleagues from the Monell Chemical Senses Center, the Feinstein Institute for Medical Research, and others, have described how ATP release is key to this sensory information path.

They found that the calcium homeostasis modulator 1 (CALHM1) protein, recently identified by the Foskett lab as a novel ion channel, is indispensable for taste via release of ATP.

"This is an example of a bona fide ATP ion channel with a clear physiological function. Now we can connect the molecular dots of sweet and other tastes to the brain," said Foskett.

Taste buds have specialized cells that express G-protein coupled receptors (GPCRs) that bind to taste molecules and initiate a complex chain of molecular events, the final step of which Foskett and collaborators show is the opening of a pore in the cell membrane formed by CALHM1. ATP molecules leave the cell through this pore to alert nearby neurons to continue the signal to the taste centers of the brain. CALHM1 is expressed specifically in sweet, bitter, and umami taste bud cells.

Advertisements

Mice in which CALHM1 proteins are absent, developed by Feinstein's Philippe Marambaud, PhD, have severely impaired perceptions of sweet, bitter and umami compounds; whereas, their recognition of sour and salty tastes remains mostly normal. The CALHM1 deficiency affects taste perception without interfering with taste cell development or overall function.

Using the CALHM1 knockout mice, team members from Monell and Feinstein tested how their taste was affected.

Advertisements

"The mice are very unusual," said Monell's Michael Tordoff, PhD. "Control mice, like humans, lick avidly for sucrose and other sweeteners, and avoid bitter compounds. However, the mice without CALHM1 treat sweeteners and bitter compounds as if they were water. They can't taste them at all."

From all lines of evidence, the team concluded that CALHM1 is an ATP-release channel required for sweet, bitter, and umami taste perception. In addition, they found that CALHM1 was also required for "nontraditional" Polycose, calcium, and aversive high-salt tastes, implying that the deficit displayed in the knockout animals might best be considered as a loss of all GPCR-mediated taste signals rather than simply sweet, bitter and umami taste.

Their research has been described in Nature.

Source-ANI