The human tongue is a marvel of sensory biology, equipped with taste buds that enable us to perceive a wide array of flavor profiles essential for survival and enjoyment. Within these taste buds reside specialized cells capable of translating chemical signals into neural impulses that the brain interprets as taste. Among these, type II cells, responsible for sensing sweet, umami, and bitter flavors, rely on mechanisms involving receptor-mediated channels. In stark contrast, type III cells, which detect sourness, appear to use classical synaptic vesicular release, a process more commonly attributed to neurons. Despite longstanding recognition of this difference, the molecular underpinnings that drive synaptic communication in sour-sensing cells have remained enigmatic.
To probe SNAP25’s function, the team engineered a conditional knockout mouse model in which the Snap25 gene was specifically ablated in epithelial-derived taste cells. Remarkably, while these SNAP25-deficient mice developed normally and survived to adulthood, they exhibited a pronounced reduction in the population of type III taste cells within two main gustatory structures: the fungiform and circumvallate papillae. In contrast, type II cells responsible for other taste modalities remained intact. This specificity indicated a unique dependence of sour-sensing cells on SNAP25.
.adsslot_fomUj64ESC{ width:728px !important; height:90px !important; }
@media (max-width:1199px) { .adsslot_fomUj64ESC{ width:468px !important; height:60px !important; } }
@media (max-width:767px) { .adsslot_fomUj64ESC{ width:320px !important; height:50px !important; } }
ADVERTISEMENT
Delving deeper into the cellular dynamics, the researchers employed 5-ethynyl-2’-deoxyuridine (EdU) tracing to monitor the birth and survival of type III cells over time. Their observations indicated that although the formation of new sour-sensitive cells persisted at normal rates, these cells failed to survive and maintain their presence within the taste buds beyond a two-week period. This suggests that the absence of SNAP25 compromises not cell generation but rather the long-term maintenance or survival of these neurons-like epithelial cells, an unexpected finding that highlights a novel survival mechanism linked to synaptic protein function.
Furthermore, electrophysiological assays of the chorda tympani nerve—responsible for transmitting taste information from the anterior tongue—demonstrated a stark reduction in neural responses to sour stimuli such as hydrochloric acid and citric acid in SNAP25 knockout mice. Responses to sweet, salty, bitter, and umami tastants, mediated largely by type II cells, were unaffected. This electrophysiological evidence confirms that SNAP25-dependent synaptic transmission is critical exclusively for the sour taste pathway.
The behavioral consequences of SNAP25 deletion in taste cells were investigated using a brief-access licking test paradigm, a quantitative measure of taste-driven aversion. While wild-type mice robustly avoided sour solutions, mutant mice with Snap25 ablation exhibited a diminished aversive response. This residual avoidance suggested the presence of additional acid-detection systems beyond gustatory synaptic transmission. To disentangle this, the researchers generated double knockout mice deficient in both Snap25 in type III cells and the proton-sensitive ion channel TRPV1 in somatosensory trigeminal neurons, which also contribute to sour sensation.
Intriguingly, these double mutants displayed nearly complete loss of behavioral aversion to sour liquids, revealing a dual-system model for sour acid detection: the gustatory system relying on SNAP25-mediated vesicular synapses in type III cells and the somatosensory system reliant on TRPV1-expressing trigeminal afferents. Remarkably, even when both pathways were disabled, high concentrations of acid could still trigger some response, hinting at yet undiscovered mechanisms or redundant safeguards in sour taste perception, likely an evolutionary adaptation to detect potentially harmful acidic substances.
At a molecular and cellular level, this study revolutionizes our understanding of taste bud physiology by demonstrating that SNAP25, traditionally considered a neuron-exclusive synaptic protein, is essential not only for neurotransmitter release from type III taste cells but also for maintaining their structural integrity and survival. This dual function underscores a broader biological principle: synaptic proteins can bridge the realms of signal transduction and cell longevity, especially in sensory epithelial tissues.
Professor Yoshida emphasizes this paradigm-shifting insight, stating, “The presence of SNAP25 is indispensable not only for neurotransmission but also for the persistence of sour-sensing cells themselves. Without its expression, these specialized cells vanish, eroding sour taste perception.” This insight invites a reevaluation of synaptic protein roles beyond classical neuronal contexts, positioning sensory epithelial cells as active participants in neural communication and self-maintenance.
Importantly, the research illuminates the unique nature of sour taste signaling, distinguishing it from other modalities by its reliance on synaptic vesicle fusion machinery. While type II cells employ channel-mediated ATP release, type III cells are neuron-like in their synaptic modus operandi, integrating canonical neurotransmitter release into peripheral sensory function. Understanding this distinction may have implications for taste disorders and for designing strategies to modulate taste perception therapeutically.
The study also opens avenues to explore how synaptic dysfunction in taste buds might contribute to sensory deficits experienced in pathological conditions, including neurodegenerative diseases or after chemotherapy. Given that SNAP25-related mechanisms are coupled to cell survival, targeting synaptic proteins may offer routes to preserve or restore sour taste function, which plays a crucial role in dietary choice and nutrition.
The team at Okayama University continues to unravel these molecular mysteries, fusing molecular genetics, electrophysiology, and behavioral science to dissect how taste receptors modulate feeding behavior and energy homeostasis. With over 70 publications, Professor Yoshida’s group stands at the forefront of taste signal transduction research, illuminating the crosstalk between sensory input and systemic physiology.
As our knowledge of taste bud architecture and function deepens, new horizons emerge—not just for basic science but also for public health, nutrition, and food sciences. Understanding how SNAP25 orchestrates sour taste transduction and cell survival may eventually translate into better diagnostic tools or treatments for taste dysfunction, enhancing life quality for affected individuals.
In conclusion, this seminal study redefines the role of synaptic proteins in sensory epithelia, spotlighting SNAP25’s dual vital function in neurotransmitter release and cellular longevity within mouse taste buds. It reveals sour taste perception as a unique sensory modality simultaneously harnessing dual detection systems and synaptic mechanisms. This transformative work enriches the conceptual landscape of neuroscience and sensory biology, laying the groundwork for future exploration of taste and beyond.
Subject of Research: Animals
Article Title: Dual functions of SNAP25 in mouse taste buds
News Publication Date: 24-Jun-2025
Web References: https://doi.org/10.1113/JP288683
Image Credits: Professor Ryusuke Yoshida of Okayama University, Japan
Keywords: Life sciences, Cell biology, Cellular neuroscience, Genetics, Molecular biology, Mouse models, Neuroscience, Neurophysiology, Neural pathways, Neurotransmission, Physiology, Sensory systems
Tags: flavor signal transductionmolecular biology of tasteneurotransmitter release in taste budsresearch on taste perceptionsensory biology of the tonguesensory cell healthSNAP25 protein functionsour taste perceptionsynaptic communication in tastetaste bud cell typestype III taste cellsvesicular release mechanisms
