SNAP to attention: the protein discerning sour flavor

Researchers have revealed a lynchpin of the mechanism behind sour taste.

In a recent mouse model study from Okayama University (Japan), a team of researchers has revealed the importance of synaptosome-associated protein 25 (SNAP25) in the mechanism responsible for sour taste. These results provide us with a better understanding of taste and also indicate that synaptic proteins may play wider roles in the maintenance of our epithelial sensory experiences.

Sensing sour-tasting foods or substances can help protect us against compounds that might harm us or damage our teeth [1], for instance, helping us differentiate between unripe and ripe fruit. Although the signaling mechanisms for one type of taste-sensing cell are well understood, for type III cells, believed to mediate sour signals, they remain unclear.

Synaptic signal transmission is driven by the SNARE complex. A key component of this is SNAP25, which is essential for synaptic vesicle fusion in neurons and in the tongue, where it is found exclusively in type III cells.

A key player in sour perception

Utilizing a murine model, the researchers selectively deleted the SNAP25 gene from epithelial-derived taste cells. These conditional knockout (cKO) mice experienced a significant loss of type III cells in two major taste bud regions. In contrast, type II cells remained unaffected.

To probe whether this reduction stemmed from impaired cell birth or degeneration, the researchers utilized immunostaining to visualize specific proteins in the taste buds and tracked new type III cell growth with EdU proliferation tracking. They found that type III cells were generated normally, but their numbers declined sharply within 14 days, indicating a defect in long-term cell maintenance rather than replenishment. The cKO mice had severely diminished responses to sour-tasting substances, but normal responses to substances tasting sweet, salty, bitter and umami, as measured by electrophysiological recordings of the chorda tympani nerve and short-term lick tests to observe their preference for or aversion to various solutions.

“Our findings show that SNAP25 has a dual function in the taste system,” commented Ryusuke Yoshida, who led the research. “Not only is SNAP25 helping these cells send sour taste signals to the brain, but it’s also crucial for the survival of the type III cells themselves. Without SNAP25, the cells eventually disappear, and without them, the ability to properly detect sourness is also lost.”

The double role of SNAP25

To further investigate the pathways involved in sensing sour, the team created double KO mice, which lacked both alleles of the Snap25 gene. The double KO mice experienced almost a complete lack of aversion to sour substances; however, they retained some response to particularly high concentrations.

“The fact that SNAP25 is indispensable not only for neurotransmitter release but also for the longevity of sour-sensing cells hints at the broader role of synaptic proteins in maintaining sensory epithelial integrity,” concluded Yoshida.