Biology subjects

Stanton, C.

Publications and source records attributed to Stanton, C..

17 recordsLinked to original sources

bioRxiv2026

Characterization of Electrophysiological and Transcriptomic Alterations in Patient-Derived Neurons from CHAMP1 Syndrome

Mutations in chromosome alignment maintaining phosphoprotein 1 (CHAMP1) have been linked to neurodevelopmental disorders characterized by intellectual disability, developmental delay, and autism spectrum disorder. However, the cellular and electrophysiological mechanisms by which CHAMP1 mutations disrupt human neuronal development remain poorly understood. In the present study, we used patient-derived induced pluripotent stem cells (iPSCs) carrying two pathogenic CHAMP1 mutations and generated neural progenitor cells (NPCs) and excitatory neurons to investigate the effects of each mutation on neuronal maturation and function, DNA repair, and gene expression. Proliferative capacity declines with CHAMP1 dosage, while DNA repair dysfunction is allele-specific. Whole-cell patch-clamp electrophysiology revealed that CHAMP1 mutant neurons exhibit significant alterations in intrinsic membrane properties during early developmental stages, including depolarized resting membrane potential, reduced action potential firing, and impaired waveform kinetics. These functional deficits were accompanied by reduced sodium and potassium current densities, suggesting impaired ion channel accumulation during neuronal maturation. Furthermore, recordings of spontaneous excitatory postsynaptic currents indicated altered synaptic activity and reduced proportions of synaptically active neurons. Morphological analyses showed that CHAMP1-deficient neurons exhibit impaired neurite outgrowth and branching, supporting a defect in neuronal maturation. Single-nucleus transcriptomic profiling further revealed delayed developmental trajectories and mutation-specific dysregulation of synaptic gene programs enriched for autism, ADHD, and epilepsy risk genes. Together, these findings demonstrate that CHAMP1 mutations disrupt multiple aspects of neuronal development, including homologous recombination (HR) dysfunction in NPCs, membrane excitability, ion channel function, and synaptic connectivity. Our results provide insights into the neurobiological consequences of CHAMP1 mutations and establish patient-derived neurons as a platform to investigate cellular pathophysiology and potential therapeutic strategies for CHAMP1-associated neurodevelopmental disorders.

neuroscience↗

bioRxiv2026

Putative Herbicolin A, an antifungal lipopeptide produced by Pantoea agglomerans APC 4211 is a promising biocontrol agent against food spoilage fungi

Fungal contamination of food with yeast and moulds is associated with major economic losses due to spoilage and also poses health risks in the form of mycotoxin production. The strain Pantoea agglomerans APC 4211 isolated from leaves of Ilex aquifolium (holly tree) has broad spectrum antifungal activity against a variety of food spoilage fungi. Genomic analysis of the strain confirmed the presence of biosynthetic gene clusters potentially encoding for the enzymatic machinery required for the production of the antifungal lipopeptide herbicolin A. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis of the cell-free supernatant (CFS) confirmed the presence of molecular masses corresponding to herbicolin A (1300.8 Da), and herbicolin B (1138 Da). Purified herbicolin A has desirable properties for biotechnological applications, including potent antifungal activity against a range of spoilage fungi, thermal stability and resistance to proteases. Herbicolin A has low cytotoxicity against epithelial cell lines and has minimum inhibitory concentrations (MICs) lower than those of some commercial antifungal drugs (0.2 - 2.5 {micro}g/ml). In a model dairy system (10% skim milk), herbicolin A demonstrated excellent solubility and stability, effectively eliminating Aspergillus niger and Penicillium notatum at a concentration of 5 {micro}g/mL. In conclusion, herbicolin A is a potent, naturally occurring antifungal agent with the potential to be applied as a biopreservative in food systems, providing a safe, clean-label, and efficient compound for synthetic preservatives replacement. HighlightsO_LIHerbicolin A has a strong potential as a natural preservative for food protection C_LIO_LIHerbicolin A shows lower MICs than several antifungal agents C_LIO_LIHerbicolin A is stable under heat and resistant to proteolytic degradation C_LIO_LIHerbicolin A has strong solubility and stability in a model dairy system C_LIO_LIHerbicolin A indicates low cytotoxicity against epithelial cell lines C_LI Data summaryThe authors confirm all supporting data, code and protocols have been provided within the article or through supplementary data files.

microbiology↗

bioRxiv2026

Infant gut microbiomes contribute to metabolic states that impact brain function

Alterations in the gut microbiome are associated with neurodevelopmental disorders, but causal mechanisms and therapeutic strategies remain undefined. Here, we demonstrate that human infant microbiomes isolated during the first six months of life drive behavioral impairments in mice and that microbiota-based interventions restore mice to normal behavior. Early-life microbiomes from twelve infants who later exhibited cognitive deficits at 2 years old (low-scoring) transferred adverse metabolic, brain, and behavioral phenotypes to mice, in contrast to microbiomes from twenty-three cognitively typical or high-scoring infants. Deficits in mice were rescued by fecal microbiota transplant from high-scoring infants or a rationally designed consortium that promoted amino acid levels. We confirmed lower fecal amino acid concentrations in low-scoring infants and replicated the association between early-life microbiome composition and cognitive outcomes in a second geographically independent infant cohort. Altogether, we discovered an early-life microbiome-mediated metabolic state causally linked to cognitive deficits and amenable to microbial intervention.

microbiology↗

bioRxiv2025

ZNFX1 uses two-component ubiquitin circuitry to quarantine viral RNA

The detection of viral RNA inside cells triggers a diverse range of antiviral responses, including global translation inhibition, interferon secretion and RNA sequestration. Mutations in the gene ZNFX1 cause severe paediatric immunodeficiencies, including chronic viral infection and autoinflammation. Here, we show that ZNFX1 is an RNA helicase with cryptic and unusual bifurcating E3 ubiquitin ligase activity. Nucleotide-dependent RNA binding stimulates ZNFX1 to generate complex ubiquitin chains via a two-component ubiquitin circuit wired in parallel, with ubiquitin flux occurring via either of two competing paths. One route produces K63-linked polyubiquitin that drives ZNFX1 aggregation and RNA entrapment; the other route produces K48-linked polyubiquitin that drives ZNFX1 turnover. RNA entrapment restricts RNA virus replication, and is reversible by deubiquitination. Patient ZNFX1 variants are defective for viral restriction, linking RNA entrapment to antiviral immunity in vivo.

biochemistry↗

bioRxiv2025

Disease-associated genetic variants can cause mutations in tissue-specific protein isoforms

Genetic variants can cause protein-coding mutations that result in disease. Variants are typically interpreted using the reference transcript for a gene. However, most human multi-exon genes encode alternative isoforms. Here, we show that coding exons in alternative isoforms harbour more population variants than exons of reference isoforms, consistent with their reduced evolutionary constraint, and that these variants are more likely to cause nonsynonymous coding mutations. Common and rare disease-associated variants mapping to alternative transcripts can lead to amino acid substitutions predicted to be structurally damaging in the corresponding protein isoform. The alternative transcripts to which disease-associated variants map demonstrate high tissue-specific expression, with many unannotated in reference human genomes, revealed only by long-read RNA-sequencing. As an example, we report an unannotated alternative transcript of the inflammasome regulator DPP9 that is lung epithelium-specific and which harbours a common genetic variant associated with severe COVID-19 and lung fibrosis. The variant causes a p.Leu8Pro missense mutation in an alternative first exon, predicted to disrupt the encoded alpha helix. These findings highlight the importance of considering alternative isoforms, their tissue-specific expression, and full-length transcripts in variant interpretation, with implications for uncovering underappreciated mechanisms of both common and rare disease.

genomics↗

bioRxiv2025

Inhibition of NF-κB Signaling by the Reactive Glycolytic Metabolite Methylglyoxal

The NF-{kappa}B family of transcription factor complexes are central regulators of inflammation, and their dysregulation contributes to the pathology of multiple inflammatory disease conditions. Accordingly, identifying pharmacological mechanisms that restrain NF-{kappa}B overactivation remains an area of key importance. Here, we demonstrate that inhibition of the glycolytic enzyme phosphoglycerate kinase 1 (PGK1) with the small molecule inhibitor CBR-470-2 results in attenuated NF-{kappa}B signaling, decreasing transcriptional output in response to several canonical NF-{kappa}B activating stimuli. Mechanistically, PGK1 inhibition promotes the accumulation of the glycolytic metabolite methylglyoxal, which crosslinks and inactivates NF-{kappa}B proteins, limiting the phosphorylation and nuclear translocation of these transcription factor complexes. This work establishes a key connection between central carbon metabolism and immune signaling and further supports the notion that PGK1 inhibition may be a viable strategy to increase cellular survival and dampen inflammation in disease.

biochemistry↗

bioRxiv2024

The Glycolytic Metabolite Methylglyoxal Covalently Inactivates the NLRP3 Inflammasome.

The NLRP3 inflammasome promotes inflammation in disease, yet the full repertoire of mechanisms regulating its activity are not well delineated. Among established regulatory mechanisms, covalent modification of NLRP3 has emerged as a common route for pharmacological inactivation of this protein. Here, we show that inhibition of the glycolytic enzyme PGK1 results in the accumulation of methylglyoxal, a reactive metabolite whose increased levels decrease NLRP3 assembly and inflammatory signaling in cells. We find that methylglyoxal inactivates NLRP3 via a non-enzymatic, covalent crosslinking-based mechanism, promoting inter- and intra-protein MICA posttranslational linkages within NLRP3. This work establishes NLRP3 as capable of sensing a host of electrophilic chemicals, both exogenous small molecules and endogenous reactive metabolites, and suggests a mechanism by which glycolytic flux can moderate the activation status of a central inflammatory signaling pathway.

cell biology↗

bioRxiv2023

Harnessing the endogenous Type I-C CRISPR-Cas system for genome editing in Bifidobacterium breve

Bifidobacterium breve, one of the main bifidobacterial species colonizing the human gastrointestinal tract in early life, has received extensive attention for its purported beneficial effects on human health. However, exploration of the mode of action of such beneficial effects exerted by B. breve is cumbersome due to the lack of effective genetic tools, which limits its synthetic biology application. Given the widespread presence of endogenous CRISPR-Cas systems in B. breve, the current study developed an endogenous CRISPR-based gene editing toolkit for genetic manipulation of B. breve. Deletion of the gene coding uracil phosphoribosyl-transferase (upp) was achieved in two different B. breve strains using this system. In addition, translational termination of uracil phosphoribosyl-transferase was successfully achieved in B. breve FJSWX38M7 by single-base substitution of the upp gene and insertion of three stop codons. The gene encoding linoleic acid isomerase (bbi) in B. breve, being a characteristic trait, was deleted after plasmid curing, which rendered it unable to convert linoleic acid into conjugated linoleic acid, demonstrating the feasibility of successive editing. This study expanded the gene manipulation toolkit of B. breve and provides a reference for functional genome editing and analysis using an endogenous CRISPR-Cas system in Bifidobacterium. ImportanceThe lack of effective genetic tools for Bifidobacterium breve is an obstacle to studying the molecular mechanisms of its health-promoting effects, hindering the development of next-generation probiotics. Here, we introduce a gene editing method based on the endogenous CRISPR-Cas system, which can achieve gene deletion, single base substitution, gene insertion and continuous gene editing in B. breve. This study will promote the excavation of functional genes and elucidation of molecular mechanisms of B. breve.

molecular biology↗

bioRxiv2023

Covalent targeting as a common mechanism for inhibiting NLRP3 inflammasome assembly.

The NLRP3 inflammasome is a cytosolic protein complex important for the regulation and secretion of inflammatory cytokines including IL-1{beta} and IL-18. Aberrant overactivation of NLRP3 is implicated in numerous inflammatory disorders. However, the activation and regulation of NLRP3 inflammasome signaling remains poorly understood, limiting our ability to develop pharmacologic approaches to target this important inflammatory complex. Here, we developed and implemented a high-throughput screen to identify compounds that inhibit inflammasome assembly and activity. From this screen we identify and profile inflammasome inhibition of 20 new covalent compounds across 9 different chemical scaffolds, as well as many known inflammasome covalent inhibitors. Intriguingly, our results indicate that NLRP3 possesses numerous reactive cysteines on multiple domains whose covalent targeting blocks activation of this inflammatory complex. Specifically, focusing on compound VLX1570, which possesses multiple electrophilic moieties, we demonstrate that this compound allows covalent, intermolecular crosslinking of NLRP3 cysteines to inhibit inflammasome assembly. Our results, along with the recent identification of numerous covalent molecules that inhibit NLRP3 inflammasome activation, suggests that NLRP3 serves as a cellular electrophile sensor important for coordinating inflammatory signaling in response to redox stress. Further, our results support the potential for covalent cysteine modification of NLRP3 for regulating inflammasome activation and activity.

biochemistry↗

bioRxiv2023

Succinylation of a KEAP1 sensor lysine promotes NRF2 activation

Crosstalk between metabolism and stress-responsive signaling is essential to maintaining cellular homeostasis. One way this crosstalk is achieved is through the covalent modification of proteins by endogenous, reactive metabolites that regulate the activity of key stress-responsive transcription factors such as NRF2. Several metabolites including methylglyoxal, glyceraldehyde 3-phosphate, fumarate, and itaconate covalently modify sensor cysteines of the NRF2 regulatory protein KEAP1, resulting in stabilization of NRF2 and activation of its cytoprotective transcriptional program. Here, we employed a shRNA-based screen targeting the enzymes of central carbon metabolism to identify additional regulatory nodes bridging metabolic pathways to NRF2 activation. We found that succinic anhydride, increased by genetic depletion of the TCA cycle enzyme succinyl-CoA synthetase or by direct administration, results in N-succinylation of lysine 131 of KEAP1 to activate NRF2 transcriptional signaling. This study identifies KEAP1 as capable of sensing reactive metabolites not only by several cysteine residues but also by a conserved lysine residue, indicating its potential to sense an expanded repertoire of reactive metabolic messengers.

cell biology↗

bioRxiv2022

The BRUTUS-LIKE E3 ligases BTSL1 and BTSL2 fine-tune transcriptional responses to balance Fe and Zn homeostasis

The mineral micronutrients zinc (Zn) and iron (Fe) are essential for plant growth and human nutrition, but interactions between the homeostatic networks of these two elements are not fully understood. Here we show that loss-of-function of BTSL1 and BTSL2, which encode partially redundant E3 ubiquitin ligases that negatively regulate Fe uptake, confers tolerance to Zn excess in Arabidopsis thaliana. Double btsl1 btsl2 mutant seedlings grown on high Zn medium accumulated similar amounts of Zn in roots and shoots as the wild type, but suppressed the accumulation of excess Fe in roots. RNA-seq analysis showed that roots of mutant seedlings had relatively higher expression of genes involved in Fe uptake (IRT1, FRO2, NAS) and in Zn storage (MTP3, ZIF1). Surprisingly, mutant shoots did not show the transcriptional Fe-deficiency response which is normally induced by Zn excess. Split-root experiments suggested that within roots the BTSL proteins act locally and downstream of systemic Fe deficiency signals. Together, our data show that constitutive low-level induction of the Fe-deficiency response protects btsl1 btsl2 mutants from Zn toxicity. We propose that BTSL protein function is disadvantageous in situations of external Zn and Fe imbalances, and formulate a general model for Zn-Fe interactions in plants. HighlightMutation of two E3 ligases that suppress iron uptake in roots also confers tolerance to zinc toxicity, identifying a regulatory point of interaction between iron and zinc homeostasis.

plant biology↗

bioRxiv2022

Individual variation in the avian gut microbiota: the influence of host state and environmental heterogeneity

The gut microbiome has important consequences for fitness, yet the complex, interactive nature of ecological factors that influence the gut microbiome has scarcely been investigated in natural populations. We sampled the gut microbiota of wild great tits (Parus major) at different life stages and across multiple conifer and mixed woodland fragments, allowing us to evaluate multiple factors that relate to within-individual gut microbiota acquisition, including habitat type, nest position and life history traits. The gut microbiota varied with both environment and life-history in ways that were largely dependent on age. Notably, it was the nestling, as opposed to the adult gut microbiota that was most sensitive to ecological variation, pointing to a high degree of developmental plasticity. Individual nestling differences in gut microbiota were consistently different (repeatable) from one to two weeks of life, driven entirely by the effect of sharing the same nest. Our findings point to important early developmental windows in which the gut microbiota are most sensitive to environmental variation and suggest reproductive timing, and hence parental quality or food availability, interact with the microbiome.

ecology↗

bioRxiv2021

Disbalance of the intestinal epithelial cell turnover and apoptosis in a rat model of sporadic Alzheimer's disease

BackgroundDyshomeostasis of the gastrointestinal (GI) system is investigated as a potential contributor to metabolic dysfunction, systemic and neuro-inflammation recognized as important pathophysiological drivers of neurodegeneration. Gastrointestinal redox dyshomeostasis and dysfunctional brain-gut incretin axis have been reported in the rat model of insulin-resistant brain state (IRBS)-driven neurodegeneration induced by intracerebroventricular administration of streptozotocin (STZ-icv). The aim was to assess i) whether GI oxidative stress is accompanied by structural and functional changes of the epithelial barrier; ii) whether the brain glucose-dependent insulinotropic polypeptide receptor (GIP-R) is also involved in redox regulation of the gut; and iii) whether the STZ-icv brain-gut axis is resistant to pharmacological inhibition of the brain GIP-R. MethodsForty three-month-old male Wistar rats were treated with 3mg/kg STZ-icv or vehicle. One month later the animals were randomized to receive either saline or 85 g/kg GIP-R inhibitor [Pro3]-GIP intracerebroventricularly and sacrificed 30 minutes later. Thiobarbituric acid reactive substances (TBARS) were measured in plasma and duodenum. Duodenal sections were subjected to morphometric analysis. Caspase-3 expression and activation were analyzed by western blot and spatial signal analysis was done by multiplex fluorescent signal amplification (MFSA). Data were analyzed by linear and linear mixed modeling, and exploration was done by principal component analysis. ResultsInhibition of the brain GIP-R decreased plasma TBARS in the controls and the STZ-icv animals and increased duodenal TBARS only in the controls. Acute inhibition of brain GIP-R affects duodenal epithelial cell, but not villus structure, while all morphometric parameters were altered in the STZ-icv-treated animals. Morphometric changes in the STZ-icv animals were accompanied by reduced levels of activated and total regulator of apoptosis - caspase-3. Acute inhibition of brain GIP-R inactivated duodenal apoptosis at the level of caspase-3 activation. ConclusionsBrain GIP-R is involved in the regulation of the systemic and duodenal redox homeostasis and epithelial function. Duodenal oxidative stress in the STZ-icv rats is accompanied by the resistance of the brain-gut GIP axis and morphological changes indicative of abnormal epithelial cell turnover and dysfunctional GI barrier. Dysfunction of the brain-gut incretin axis might be an important etiopathogenetic factor in neurodegeneration and a potential pharmacological target.

neuroscience↗

bioRxiv2021

Honeybees exposure to veterinary drugs: how the gut microbiota is affected

Several studies have outlined that a balanced gut microbiota offers metabolic and protective functions supporting honeybee health and performances. The present work contributes to increasing knowledge on the impact on the honeybee gut microbiota of the administration of three different veterinary drugs (oxytetracicline, sulphonamides and tylosin). The trial was designed with a semi-field approach in micro-hives containing about 500 bees, i.e. in experimental conditions as close as possible to real hives considering the restrictions on the use of antibiotics; 6 replicates were considered for each treatment plus the control. The absolute abundance of the major gut microbial taxa in newly eclosed individuals was studied with qPCR and next generation sequencing. Antimicrobial resistance genes for the target antibiotics were also monitored using a qPCR approach. The results showed that none of the veterinary drugs altered the total amount of gut bacteria, but qualitative variations were observed. Tylosin treatment determined a significant decrease of - and {beta}-diversity indexes and a strong the depletion of the rectum population (lactobacilli and bifidobacteria) while favoring the hindgut population (Gilliamella, Snodgrassella and Frischella spp.). Major changes were also observed in honeybees treated with sulphonamides, with a decrease in Bartonella and Frischella core taxa an increase of Bombilactobacillus spp. and Snodgrassella spp. Conversely, minor effects were observed in oxytetracycline treated honeybees. Monitoring of antibiotic resistance genes confirmed that honeybees represent a great reservoir of tetracycline resistance genes. Tetracycline and sulphonamides resistant genes tended to increase in the gut microbiota population upon antibiotic administration. ImportanceThis study investigates the impact of the three most widely used antibiotics in the beekeeping sector (oxytetracycline, tylosin and sulphonamides) on the honeybee gut microbiota and on the spread of antibiotic resistance genes. The research represents an advancement to the present literature considering that tylosin and sulphonamides effect on the gut microbiota has never been studied. Another original aspect lies in the experimental approach used, as the study looks at the impact of veterinary drugs and feed supplements 24 days after the beginning of the administration, thus exploring perturbations in newly eclosed honeybees, instead of the same treated honeybee generation. Moreover, the study is not performed with cage tests but in micro-hives thus reaching conditions closer to real hives. The study reaches the conclusion that tylosin and sulfonamides determine major changes in some core members and that antibiotic resistance genes for tetracycline and sulphonamides increase upon antibiotic treatment.

microbiology↗

bioRxiv2020

A time-lagged association between the gut microbiome, nestling growth and nestling survival in wild great tits

O_LINatal body mass is a key predictor of viability and fitness in many animals. While variation in body mass and therefore juvenile viability may be explained by genetic and environmental factors, emerging evidence points to the gut microbiota as an important factor influencing host health. The gut microbiota is known to change during development, but it remains unclear whether the microbiome predicts fitness, and if it does, at which developmental stage it affects fitness traits. C_LIO_LIWe collected data on two traits associated with fitness in wild nestling great tits (Parus major): weight and survival to fledging. We characterised the gut microbiome using 16S rRNA sequencing from nestling faeces and investigated temporal associations between the gut microbiome and fitness traits across development at day 8 (D8) and day 15 (D15) post-hatching. We also explored whether particular microbial taxa were indicator species that reflected whether nestlings survived or not. C_LIO_LIThere was no link between mass and microbial diversity on D8 or D15. However, we detected a time-lagged relationship where weight at D15 was negatively associated with the microbial diversity at D8, controlling for weight at D8, therefore reflecting relative weight gain over the intervening period. C_LIO_LIIndicator species analysis revealed that specificity values were high and fidelity values were low, suggesting that indicator taxa were primarily detected within either the survived or not survived groups, but not always detected in birds that either survived or died. Therefore these indicator taxa may be sufficient, but not necessary for determining either survival or mortality, perhaps owing to functional overlap in microbiota. C_LIO_LIWe highlight that measuring microbiome-fitness relationships at just one time point may be misleading, especially early in life. Instead, microbial-host fitness effects may be best investigated longitudinally to detect critical development windows for key microbiota and host traits associated with neonatal weight. Our findings should inform future hypothesis testing to pinpoint which features of the gut microbial community impact on host fitness, and when during development this occurs. Such confirmatory research will shed light on population level processes and could have the potential to support conservation. C_LI

ecology↗

bioRxiv2019

Diet-induced changes to host gut microbiota are linked to foraging innovation in a wild bird.

The microbial community in the gut is influenced by environmental factors, especially diet, which can moderate host behaviour through the microbiome-gut-brain axis. However, the ecological relevance of microbiome-mediated behavioural plasticity in wild animals is unknown. We presented wild-caught great tits (Parus major) with a problem-solving task and showed that performance was weakly associated with variation in the gut microbiome. We then manipulated the gut microbiome by feeding birds one of two diets that differed in their relative levels of fat, protein and fibre content: an insect diet (low content), or a seed diet (high content). Microbial communities were less diverse among individuals given the insect compared to those on the seed diet. Individuals were less likely to problem-solve after being given the insect diet, and the same microbiota metrics that were altered as a consequence of diet were also those that correlated with variation in problem solving performance. Although the effect on problem-solving behaviour could have been caused by motivational or nutritional differences between our treatments, our results nevertheless raise the possibility that dietary induced changes in the gut microbiota could be an important mechanism underlying individual behavioural plasticity in wild populations.

ecology↗

bioRxiv2018

TACAN is an essential component of the mechanosensitive ion channel responsible for pain sensing

Mechanotransduction, the conversion of mechanical stimuli into electrical signals, is a fundamental process underlying several physiological functions such as touch and pain sensing, hearing and proprioception. This process is carried out by specialized mechanosensitive ion channels whose identities have been discovered for most functions except pain sensing. Here we report the identification of TACAN (Tmem120A), an essential subunit of the mechanosensitive ion channel responsible for sensing mechanical pain. TACAN is expressed in a subset of nociceptors, and its heterologous expression increases mechanically-evoked currents in cell lines. Purification and reconstitution of TACAN in synthetic lipids generates a functional ion channel. Finally, knocking down TACAN decreases the mechanosensitivity of nociceptors and reduces behavioral responses to mechanical but not to thermal pain stimuli, without affecting the sensitivity to touch stimuli. We propose that TACAN is a pore-forming subunit of the mechanosensitive ion channel responsible for sensing mechanical pain.

neuroscience↗