Newly Identified Protein Solves Mystery Of Taste Perception
redOrbit Staff & Wire Reports – Your Universe Online
A consortium of scientists has identified a new protein regulator of taste, findings that help unlock the mystery of exactly how cells transmit taste information to the brain for three out of the five primary taste types.
The researchers identified CALHM1, a channel in the walls of taste receptor cells, as a necessary component in the process of sweet, bitter, and umami (savory) taste perception.
The other two taste types, sour and salt, use different mechanisms to send taste information to the brain.
The investigators found that the CALHM1 (calcium homeostasis modulator 1) channel protein, which spans a taste bud cell’s outer membrane to allow ions and molecules in and out, releases ATP — the body’s main fuel source — to make a neural taste connection.
“This is an example of a bona fide ATP ion channel with a clear physiological function,” said Kevin Foskett, professor of Physiology at the Perelman School of Medicine at University of Pennsylvania.
Foskett was among the multidisciplinary consortium of 19 researchers from nine institutions who worked on the study.
“Now we can connect the molecular dots of sweet and other tastes to the brain,” he said.
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 colleagues 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.
Mice in which CALHM1 proteins are absent, developed by Philippe Marambaud of the Feinstein Institute for Medical Research, 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, the scientists tested how their taste was affected.
“The mice are very unusual,” said Michael Tordoff of the Monell Chemical Senses Center.
“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.”
Based on all the evidence, the researchers concluded that CALHM1 is an ATP-release channel required for sweet, bitter, and umami taste perception.
They also found that CALHM1 was 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.
Interestingly, CALHM1 was originally implicated in Alzheimer’s disease, although the link is now less clear. In 2008, co-author Marambaud identified CALHM1 as a risk gene for Alzheimer’s, having discovered that a CALHM1 genetic variant was more common among people with Alzheimer’s, and led to a partial loss of function.
The researchers also found that this novel ion channel is strongly expressed in the hippocampus, a brain region necessary for learning and memory. However, there has been no connection found so far between taste perception and Alzheimer’s risk, although Marambaud suspects that scientists will begin testing this hypothesis.
The findings are published in the March issue of journal Nature.