The tongue contains numerous taste buds—tiny sensory organs responsible for detecting taste. Taste buds consist of specialized cells that translate chemical stimuli into neural signals. Among them, type II cells, which respond to sweet, umami, and bitter stimuli, utilize channel-based signal transmission. In contrast, type III cells are believed to mediate sour signals via synaptic vesicle release. While the signaling mechanisms of type II cells are well-characterized, the process of vesicular synaptic transmission in type III cells is poorly understood.
Synaptic signal transmission relies on the SNARE complex, a group of proteins that mediate vesicle fusion. Synaptosome-associated protein 25 (SNAP25), a key component of this complex, is essential for synaptic vesicle fusion in neurons. In the tongue, SNAP25 is found exclusively in type III cells. What role does SNAP25 play in sour taste transmission? How does it contribute to synaptic vesicular release in type III cells?
Now, a team of researchers led by Professor Ryusuke Yoshida and Assistant Professor Kengo Horie from the Department of Oral Physiology at Okayama University, Japan, have addressed these questions in a new study published in The Journal of Physiology and made available online on June 24, 2025.
The team developed a mouse model in which the Snap25 gene was selectively deleted from epithelial-derived taste cells. These conditional knockout (cKO) mice survived into adulthood, but with a significant loss of type III cells in both the fungiform and circumvallate papillae—two major taste bud regions on the tongue. In contrast, type II cells remained unaffected. To probe whether this reduction stemmed from impaired cell birth or degeneration, the researchers used ‘EdU tracing’ to label newly formed type III cells. 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.
Electrophysiological recordings of the chorda tympani nerve revealed that Snap25-deficient mice had severely diminished responses to sour-tasting substances, such as hydrochloric acid and citric acid. Responses to sweet, salty, bitter, and umami tastants were unaffected, indicating that the observed deficit was specific to sour taste.
“Our findings show that SNAP25 has a dual function in the taste system,” says Prof. Yoshida. “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.”
To examine how SNAP25 affects behavior, the researchers used a short-term lick test. Normal mice avoided sour solutions, but Snap25 cKO mice showed less aversion. Still, some avoidance remained, suggesting that other pathways might be involved. To probe this, the team created double KO mice—lacking both alleles of the Snap25 gene in type III cells—and transient receptor potential vanilloid 1 (Trpv1), a proton-sensitive channel in somatosensory trigeminal neurons. Double KO mice showed a much higher propensity for licking sour substances—a near-complete loss of sour aversion. These findings point to dual detection systems: one gustatory, via Type III cells and SNAP25-mediated synapses, and one somatosensory, via TRPV1-expressing trigeminal fibers.
Interestingly, even these double KO mice retained some response to high concentrations of acid, hinting at the existence of additional sour-detection mechanisms. These could be evolutionary redundancies that ensure harmful acidic substances can still be detected even if one taste perception pathway fails. The findings of this study show how sour taste perception differs from other tastes by uniquely depending on neuron-like vesicular synapses. In doing so, the study reinforces that peripheral sensory cells may use classic synaptic mechanisms not only to transmit information but also support cell longevity.
“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,” concludes Prof. Yoshida.
About Okayama University, Japan
As one of the leading universities in Japan, Okayama University aims to create and establish a new paradigm for the sustainable development of the world. Okayama University offers a wide range of academic fields, which become the basis of the integrated graduate schools. This not only allows us to conduct the most advanced and up-to-date research, but also provides an enriching educational experience.
Website: https://www.okayama-u.ac.jp/index_e.html
About Professor Ryusuke Yoshida from Okayama University, Japan
Prof. Ryusuke Yoshida is a professor in the Department of Oral Physiology at the Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Japan. He also serves as a vice‑director of the Advanced Research Center for Oral and Craniofacial Sciences (ARCOCS). Prof. Yoshida did his bachelor’s, master’s, and doctoral studies at Kobe University, Japan. Before becoming a professor at Okayama University, he was a faculty member at Kyushu University. Prof. Yoshida’s research involves studying the molecular mechanisms of taste and how taste receptors regulate energy homeostasis, feeding behavior, and obesity. He has over 70 publications to his name.
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