Biomedical subjects

Jing Wang

Publications and source records attributed to Jing Wang.

At least 37 records · Page 2Linked to original sources

PubMed2025

Coordinated regulation of glutathione S-transferases confers metabolic flexibility in multi-insecticide-resistant Frankliniella occidentalis (Pergande).

INTRODUCTION: The evolution of multi-insecticide resistance in insect pests threatens global food security. Although glutathione S-transferases (GSTs) are implicated in detoxification, the coordinated mechanism by which specific gene subfamilies interact to confer broad-spectrum resistance remains inadequately characterized. OBJECTIVE: To dissect the functional allocation and cooperation of GST subfamilies in multi-insecticide-resistant strains of Frankliniella occidentalis. METHODS: We integrated comparative genomics (20 GST genes cloned), transcriptomics (qRT-PCR), RNAi-mediated silencing, molecular docking (AutoDock Vina), and in vitro metabolism assays (UPLC-MS/MS) across susceptible and resistant thrips strains. RESULTS: The two resistant strains (NIL-R and FS-R) exhibited moderate to high resistance to five insecticides (chlorfenapyr, emamectin benzoate, spinetoram, spinosad, and thiamethoxam), accompanied by significantly elevated GSTs activity. Phylogenetic analysis indicates that GSTs include 10 conserved delta and 7 diverse sigma members. The sigma subfamily has undergone a marked expansion due to gene duplication. Delta (FoGSTd1, d4, and d9) and sigma (FoGSTs1, s2, and s6) genes were significantly up-regulated in the resistant strains. RNAi showed specialized functional allocation among GSTs: delta GSTs mediated resistance to spinosad and chlorfenapyr, sigma GSTs were responsible for thiamethoxam resistance, and notably, cooperation between these subfamilies contributed to resistance against emamectin benzoate and spinetoram. Molecular docking and in vitro metabolism assays of FoGSTd9 and FoGSTs1 proteins further supported the functional allocation and cooperative roles of GST subfamilies. CONCLUSION: Our results indicate that F. occidentalis may coordinate GST subfamilies to achieve metabolic flexibility in response to multi-insecticide pressure. This survival strategy, mediated by mechanistic functional allocation and cooperative interactions among subfamilies, may contribute to energy conservation and reduced adaptive costs. Disruption of this coordinated mechanism represents a potential approach for overcoming resistance in agricultural pest populations.

Animals↗

PubMed2025

Efficacy of esketamine in reducing nausea and vomiting after anesthesia: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Postoperative nausea and vomiting (PONV) are significant perioperative challenges. This study evaluated the efficacy of perioperative esketamine in preventing PONV. MATERIALS AND METHODS: We systematically searched Embase, PubMed, Web of Science, and the Cochrane Library from inception to August 2025 for randomized controlled trials investigating the effect of perioperative esketamine on PONV. The primary outcome was PONV incidence. Secondary outcomes included time to first flatus, postoperative pain degree, anxiety scores, agitation, anesthesia recovery time, and post-anesthesia care unit (PACU) stay duration. Data were analyzed using RevMan 5.4 and STATA 15.0 software. Sensitivity and subgroup analyses were performed to assess result stability and explore potential sources of heterogeneity. RESULTS: Thirty-eight randomized trials (3,425 patients) were included. Esketamine reduced the risk of nausea (RR=0.69, 95% CI: 0.53-0.90) and vomiting (RR=0.75, 95% CI: 0.57-0.98), shortened time to first flatus (SMD=-0.81, 95% CI: -1.48 to -0.15), and decreased rescue analgesic needs within 2 days (SMD=0.32, 95% CI: 0.2-0.5). However, it prolonged anesthesia recovery time (SMD=0.97, 95% CI: 0.28-1.67) and PACU stay (SMD=0.76, 95% CI: 0.27-1.26). CONCLUSIONS: Perioperative esketamine may reduce PONV and aid gastrointestinal recovery, but its potential to delay anesthesia recovery and PACU discharge requires consideration. Further studies are needed to clarify its risk-benefit profile. DATE OF FIRST SUBMISSION TO PROSPERO: 10 March 2024. DATE OF THE START OF STUDY SCREENING AGAINST ELIGIBILITY CRITERIA: 21 March 2024.

Humans↗

PubMed2025

Primulina pan-genome reveals differential gene retention following whole-genome duplications and provides insights into edaphic specialization.

Primulina, a genus of >200 species specialized to extreme soils, provides a model for edaphic adaptation. We assemble seven genomes and construct a pan-genome spanning nine species from karst, Danxia, and acidic soils. Comparative analyses reveal that karst-adapted species have smaller genomes. Two lineage-specific whole-genome duplications (WGDs) exhibit biased duplicate loss in large gene families but preferential retention of transcription factors, indicating combined adaptive and nonadaptive forces. Pan-genome analyses identify ion channel and transporter genes enriched in variant hotspots and under positive selection in karst lineages. Candidate genes for drought and salt stress tolerance include ABC transporters and ion channels. Notably, an ABC transporter shows positive selection in karst species and unique structural variation in non-karst species. Together, our findings show that genome downsizing, biased post-WGD retention, and evolution of ion-transport pathways shape adaptation to extreme soils. The Primulina pan-genome provides a resource for dissecting mechanisms underlying edaphic specialization.

Gene Duplication↗

PubMed2025

Efficient site-specific integration of kilobase-length DNA fragments in plant cells via Kp03 recombinase.

Targeted insertion of large DNA sequences into plant genomes remains a major challenge in synthetic biology. Here, we evaluate the large serine recombinase Kp03 for site-specific integration of DNA fragments in rice and Arabidopsis. In transient protoplast assays, Kp03 mediates efficient insertion of donor DNA up to 27.3 kilobases (kb), with plasmid integration efficiencies reaching 99.1% for fragments up to 3.4 kb. Truncation experiments reveal that a minimal 15-bp attB sequence is necessary for integration. As a proof of concept, Kp03 successfully incorporates a 3.4-kb donor DNA into the rice genome at a locus containing this minimal attB sequence. Moreover, in rice callus, combining Kp03 with the NM-PE genome editing system to install a 26-bp attB site enables targeted integration of a 3.4-kb donor at the desired genomic locus. These findings establish Kp03 as a versatile tool for plant genome engineering, with broad applications for synthetic biology.

Oryza↗

PubMed2025

Harnessing Landscape Genomics to Evaluate Genomic Vulnerability and Future Climate Resilience in an East Asia Perennial.

In this era of rapid climate change, understanding the adaptive potential of organisms is imperative for buffering biodiversity loss. Genomic forecasting provides invaluable insights into population vulnerability and adaptive potential under diverse climatic conditions, thereby facilitating management interventions and bolstering shaping species-specific germplasm conservation strategies. We primarily employed landscape genomics approaches, leveraging single-nucleotide polymorphisms obtained through whole-genome resequencing of 201 individuals across 43 Rheum palmatum complex populations, to pinpoint adaptive variation and its significance in the context of future climates, delineate seed zones, and establish guidelines for ex situ germplasm conservation. The species complex exhibited strong signatures of local adaptation and differential genomic vulnerabilities across its distribution range, with eastern lineage populations facing significant maladaptation risks under future climate scenarios. Using diverse datasets of putatively adaptive loci and climate change scenarios, we delineated three distinct seed zones within the species' range, estimated varying sample sizes per zone to capture most adaptive diversity, and predicted shifts in seed zone centroids ranging from 48.3 to 359.3 km from historical distributions to mitigate climate change impacts. Collectively, our findings underscore the importance of integrating genomic and environmental data to forecast the adaptive trajectory of an East Asian perennial under anticipated climate changes, guide seed zone delineation for germplasm conservation and enhance population resilience. These results provide a blueprint for designing targeted conservation strategies and restoration plans in other imperilled species.

Climate Change↗

PubMed2025

Cancer-induced nerve injury promotes resistance to anti-PD-1 therapy.

Perineural invasion (PNI) is a well-established factor of poor prognosis in multiple cancer types1, yet its mechanism remains unclear. Here we provide clinical and mechanistic insights into the role of PNI and cancer-induced nerve injury (CINI) in resistance to anti-PD-1 therapy. Our study demonstrates that PNI and CINI of tumour-associated nerves are associated with poor response to anti-PD-1 therapy among patients with cutaneous squamous cell carcinoma, melanoma and gastric cancer. Electron microscopy and electrical conduction analyses reveal that cancer cells degrade the nerve fibre myelin sheets. The injured neurons respond by autonomously initiating IL-6- and type I interferon-mediated inflammation to promote nerve healing and regeneration. As the tumour grows, the CINI burden increases, and its associated inflammation becomes chronic and skews the general immune tone within the tumour microenvironment into a suppressive and exhaustive state. The CINI-driven anti-PD-1 resistance can be reversed by targeting multiple steps in the CINI signalling process: denervating the tumour, conditional knockout of the transcription factor mediating the injury signal within neurons (Atf3), knockout of interferon-α receptor signalling (Ifnar1-/-) or by combining anti-PD-1 and anti-IL-6-receptor blockade. Our findings demonstrate the direct immunoregulatory roles of CINI and its therapeutic potential.

Animals↗

PubMed2025

MYC Regulates a DNA Repair Gene Expression Program in Small Cell Carcinoma of the Ovary, Hypercalcemic Type.

BACKGROUND/OBJECTIVES: SCCOHT is an aggressive and often fatal cancer that belongs to the ~20% of cancers defined by mutations to subunits of the SWI/SNF chromatin remodeling complex. In SCCOHT, mutations to the SMARCA4 gene, which encodes the SWI/SNF ATPase BRG1, are sufficient to impair SWI/SNF function. This single genetic lesion leads to a cascade of events that promote tumorigenesis, some of which may involve the intersection of SWI/SNF with oncogenic pathways such as those regulated by the MYC oncogene. In SCCOHT tumors and other cancers marked by SWI/SNF subunit mutation, MYC target genes are recurrently activated, pointing to a relationship between SWI/SNF and MYC that has yet to be fully explored. METHODS: In this study, we investigate the contribution of MYC to SCCOHT biology by performing a combination of chromatin binding and transcriptome assays in genetically engineered SCCOHT cell lines, with subsequent validation using patient tumor expression data. RESULTS: We find that MYC binds to thousands of active promoters in the BIN-67 SCCOHT cell line and that the depletion of MYC results in a broad range of gene expression changes with a notable effect on the expression of genes related to DNA repair. We uncover an MYC-regulated DNA repair gene expression program in BIN-67 cells that is antagonized by BRG1 reintroduction. Finally, we identify a DNA repair gene signature that is upregulated in SCCOHT tumors and in tumors defined by loss of the SWI/SNF subunit SNF5. CONCLUSIONS: Collectively, these data implicate MYC as a robust regulator of DNA repair gene expression in SCCOHT and lay a foundation for future studies focused on interrogating the relationship between BRG1 and MYC.

ATR↗

PubMed2025

Evolutionary Genomics Unravels the Responses and Adaptation to Climate Change in a Key Alpine Forest Tree Species.

Despite widespread biodiversity loss, our understanding of how species and populations will respond to accelerated climate change remains limited. In this study, we integrate population genomics, experimental evolution, and environmental modeling to elucidate the evolutionary responses to climate change in Populus lasiocarpa, a key alpine forest tree species primarily distributed in the mountainous regions of a global biodiversity hotspot. Over historical timescales, our findings demonstrate that demographic dynamics, divergent selection, and long-term balancing selection have shaped and maintained genetic variation within and between populations. In examining genomic signatures of contemporary climate adaptation, we found that haplotype blocks, potentially caused by inversion polymorphisms that suppress recombination, are linked to enriched combinations of locally adaptive environmental variations. We further assessed the relative contributions of environmentally induced plastic responses, constitutive expression divergence between genetic clusters, and their interactions in driving gene expression variation and divergence. Notably, we observed a strong correlation between sequence divergence and constitutive differential expression among genetic clusters. Finally, by incorporating genetic adaptation, migration, and genetic load into our predictions of population-level climate change risks, we identified western populations-primarily distributed in the Hengduan Mountains, a region known for its environmental heterogeneity and significant biodiversity-as the most vulnerable to climate change. These populations should be prioritized for conservation and management. Overall, our study advances the understanding of the relative roles of long-term natural selection, local environmental adaptation, and immediate plastic expression changes in shaping the responses of natural populations of keystone species to climate change.

Climate Change↗

PubMed2025

LncRNA C5orf64 polymorphisms (rs12518552 and rs2950218) decreases pulmonary tuberculosis susceptibility.

BACKGROUND: Pulmonary tuberculosis (PTB) remains a significant global health issue, with genetic factors playing a crucial role in susceptibility. Long noncoding RNA (lncRNA) C5orf64 has been implicated in immune responses and cancer, but its association with PTB risk has not been fully explored. METHODS: Genomic DNA was extracted from peripheral blood samples of 955 participants (474 PTB cases and 481 controls). Rs12518552 and rs2950218 in C5orf64 were genotyped using the Agena MassARRAY system. Logistic regression analysis was performed to assess the association between these polymorphisms and PTB risk. Stratified analysis was conducted to evaluate the influence of age, gender, and smoking status. RESULTS: Rs12518552-G (OR = 0.82, p = 0.034) and rs2950218-T (OR = 0.77, p = 0.012) were associated with a reduced PTB risk. Stratified analysis revealed that rs12518552 was associated with a protective effect against PTB in individuals over 40 years old (OR = 0.73, p = 0.024), females (OR = 0.77, p = 0.034), and non-smokers (OR = 0.78, p = 0.040), and rs2950218 was also associated with a reduced PTB risk in individuals over 40 years old (OR = 0.73, p = 0.040), females (OR = 0.72, p = 0.046), and non-smokers (OR = 0.72, p = 0.011). CONCLUSION: C5orf64 polymorphisms, particularly rs12518552 and rs2950218, are associated with a reduced risk of PTB. These findings suggest that C5orf64 polymorphisms contribute to genetic susceptibility to PTB, with implications for PTB targeted screening and personalized therapeutic strategies.

Humans↗

PubMed2025

Efficient and multiplexed somatic genome editing with Cas12a mice.

Somatic genome editing in mouse models has increased our understanding of the in vivo effects of genetic alterations. However, existing models have a limited ability to create multiple targeted edits, hindering our understanding of complex genetic interactions. Here we generate transgenic mice with Cre-regulated and constitutive expression of enhanced Acidaminococcus sp. Cas12a (enAsCas12a), which robustly generates compound genotypes, including diverse cancers driven by inactivation of trios of tumour suppressor genes or an oncogenic translocation. We integrate these modular CRISPR RNA (crRNA) arrays with clonal barcoding to quantify the size and number of tumours with each array, as well as the impact of varying the guide number and position within a four-guide array. Finally, we generate tumours with inactivation of all combinations of nine tumour suppressor genes and find that the fitness of triple-knockout genotypes is largely explainable by one- and two-gene effects. These Cas12a alleles will enable further rapid creation of disease models and high-throughput investigation of coincident genomic alterations in vivo.

Animals↗

PubMed2025

Recognizing the evolution of clinical syndrome spectrum progression in individuals with single large-scale mitochondrial DNA deletion syndromes (SLSMDS).

PURPOSE: Single large-scale mtDNA deletions (SLSMD) result in single large-scale deletion syndromes (SLSMDS). SLSMDS presentations have classically been recognized to encompass at least 3 distinct clinical phenotypes: Pearson syndrome (PS), Kearns-Sayre syndrome (KSS), and chronic progressive ophthalmoplegia. METHODS: A facilitated review of electronic medical records, manual charts, and Research Electronic Data Capture research databases was performed to complete a retrospective natural history study of 30 participants with SLSMDS in a single health system between 2002 and 2020. The evaluated characteristics included genetic and clinical laboratory test values, growth parameters, signs and symptoms, demographics, and patient-reported outcome measures of fatigue, quality of life, and overall function. RESULTS: Detailed cohort characterization highlighted that a recurrent deleted region involving MT-ND5 (HGNC:7641) occurs in 96% of participants with SLSMDS regardless of the clinical phenotype, which tends to evolve over time. Higher blood heteroplasmy correlated with an earlier age of onset. Growth differentiation factor 15 levels were elevated in all participants with SLSMDS. A history of PS was associated with poor survival prognosis. Furthermore, increased fatigue and decreased quality of life have been reported in patients with SLSMD with advanced age. CONCLUSION: A retrospective natural history study of patients with SLSMDS demonstrated the evolution of classically considered PS, Kearns-Sayre syndrome, and chronic progressive ophthalmoplegia clinical presentations in affected individuals, which may inform future clinical trial developments.

Humans↗

PubMed2025

Rice transcription factor bHLH25 confers resistance to multiple diseases by sensing H2O2.

Hydrogen peroxide (H2O2) is a ubiquitous signal regulating many biological processes, including innate immunity, in all eukaryotes. However, it remains largely unknown that how transcription factors directly sense H2O2 in eukaryotes. Here, we report that rice basic/helix-loop-helix transcription factor bHLH25 directly senses H2O2 to confer resistance to multiple diseases caused by fungi or bacteria. Upon pathogen attack, rice plants increase the production of H2O2, which directly oxidizes bHLH25 at methionine 256 in the nucleus. Oxidized bHLH25 represses miR397b expression to activate lignin biosynthesis for plant cell wall reinforcement, preventing pathogens from penetrating plant cells. Lignin biosynthesis consumes H2O2 causing accumulation of non-oxidized bHLH25. Non-oxidized bHLH25 switches to promote the expression of Copalyl Diphosphate Synthase 2 (CPS2), which increases phytoalexin biosynthesis to inhibit expansion of pathogens that escape into plants. This oxidization/non-oxidation status change of bHLH25 allows plants to maintain H2O2, lignin and phytoalexin at optimized levels to effectively fight against pathogens and prevents these three molecules from over-accumulation that harms plants. Thus, our discovery reveals a novel mechanism by which a single protein promotes two independent defense pathways against pathogens. Importantly, the bHLH25 orthologues from available plant genomes all contain a conserved M256-like methionine suggesting the broad existence of this mechanism in the plant kingdom. Moreover, this Met-oxidation mechanism may also be employed by other eukaryotic transcription factors to sense H2O2 to change functions.

Hydrogen Peroxide↗

PubMed2025

Paternally Expressed Gene 10 Promoter Methylation Level as a Predictor of HBeAg Seroconversion in Chronic Hepatitis B Patients.

The management of chronic hepatitis B (CHB) encounters challenges like suboptimal antiviral response and the lack of predictive biomarkers. In this study, the role of paternally expressed gene 10 (PEG10) in hepatitis B e antigen (HBeAg) seroconversion (HBeAg SC) was explored to identify a therapeutic target and predictive model. In total, 349 participants were recruited, and 141 HBeAg-positive patients were followed up after 48 weeks of antiviral therapy. Key genes were screened by machine learning algorithms (BORUTA, RF and LASSO). PEG10 mRNA, promoter methylation and plasma levels were examined. The effect of PEG10 was assessed by logistic regression, and HBeAg SC was predicted by nomograms. HBeAg-positive patients showed markedly elevated PEG10 mRNA expression (p < 0.001), which correlated strongly with major virological markers such as HBV DNA (r = 0.520, p < 0.001), HBeAg (r = 0.490, p < 0.001) and HBsAg (r = 0.400, p < 0.001). In addition, HBeAg-positive patients exhibited a significant reduction in PEG10 promoter methylation levels compared with controls (p < 0.001). According to logistic regression analysis, PEG10 promoter methylation status was an independent predictor of HBeAg SC. The predictive nomogram incorporating PEG10 promoter methylation ratio (PMR), albumin (ALB), aspartate aminotransferase (AST) and HBeAg demonstrated excellent clinical predictive value (area under curve (AUC) = 0.895,95% confidence interval (CI): 0.808 ~ 0.963). The methylation status of the PEG10 promoter represents a promising biomarker for the prediction of HBeAg SC in patients with CHB. CLINICAL TRIAL REGISTRATION: Not applicable.

Humans↗

PubMed2025

Characterization of FLOWERING LOCUS T-related genes and their putative gene regulatory network in semi-winter Brassica napus cultivar Zhongshaung11.

In many species, FLOWERING LOCUS T (FT)-like genes promote the floral transition by integrating environmental signals, in particular photoperiod, and internal cues. Here we show that Brassica napus contains six FT-like genes and two pseudogenes belonging to three orthogroups. All B. napus FT-like genes induce early flowering when expressed at the shoot apical meristems of Arabidopsis thaliana ft mutants; however, BnaFT.C6 and non-orthologous FT-like genes do not encode fully functional mobile florigens. In the case of BnFT.C6, the functional change is associated with a T to C amino acid change that is restricted to semi-winter accessions. Expression of orthologs of FT is photoperiod-dependent, and two distal enhancers are conserved; however, the homeologs BnaFT.A7 and BnaFT.C6 show rearrangements of DNA motifs binding NF-Y/CO and NF-Y transcriptional activator complexes between the promoter and downstream enhancers. Motif rearrangements correlate with differences in tissue-specific expression. Furthermore, homeologs with rearranged motifs could not be transactivated by B. napus CO in transient assays, although they show LD photoperiod-dependent expression. We propose that differential diurnal expression of NF-Y genes contributes to the photoperiod-dependent regulation of B. napus FT genes.

Brassica napus↗

PubMed2025

Comparative analysis of DREB gene family in buckwheat: the role of FtDREB02 in the delphinidin biosynthesis and drought stress response.

Dehydration response element binding (DREB) transcription factors play a pivotal role in plant abiotic stress responses, but its evolutionary and functional characterization in buckwheat remains unexplored. Here, we conducted a comprehensive analysis of the DREB gene family across three buckwheat species, revealing segmental duplication as the primary driver of family expansion and potential purifying selection during evolution. A FtDREB02 gene, classified as group A2, was identified through genome-wide association analysis (GWAS) on drought tolerance and delphinidin content. Functional validation in Arabidopsis thaliana and the hairy root of Tartary buckwheat (Fagopyrum tataricum) demonstrated that overexpression of this gene promotes delphinidin biosynthesis and enhances plant resistance to water scarcity. Through the integration of DAP-seq and PEG transcriptome cluster analysis, a FtANS candidate was screened. Functional studies showed that FtDREB02 regulates delphinidin content by binding directly to DRE elements of the FtANS promoter. This research identifies and comprehensively analyzes the DREB family within buckwheat species, elucidating the regulatory mechanisms of FtDREB02 in controlling flavonoid biosynthesis and drought resistance, providing potential genetic resources for breeding buckwheat varieties with excellent agronomic traits.

Anthocyanins↗

PubMed2023

MCT4-dependent lactate secretion suppresses antitumor immunity in LKB1-deficient lung adenocarcinoma.

Inactivating STK11/LKB1 mutations are genomic drivers of primary resistance to immunotherapy in KRAS-mutated lung adenocarcinoma (LUAD), although the underlying mechanisms remain unelucidated. We find that LKB1 loss results in enhanced lactate production and secretion via the MCT4 transporter. Single-cell RNA profiling of murine models indicates that LKB1-deficient tumors have increased M2 macrophage polarization and hypofunctional T cells, effects that could be recapitulated by the addition of exogenous lactate and abrogated by MCT4 knockdown or therapeutic blockade of the lactate receptor GPR81 expressed on immune cells. Furthermore, MCT4 knockout reverses the resistance to PD-1 blockade induced by LKB1 loss in syngeneic murine models. Finally, tumors from STK11/LKB1 mutant LUAD patients demonstrate a similar phenotype of enhanced M2-macrophages polarization and hypofunctional T cells. These data provide evidence that lactate suppresses antitumor immunity and therapeutic targeting of this pathway is a promising strategy to reversing immunotherapy resistance in STK11/LKB1 mutant LUAD.

Animals↗

PubMed2016

Substituting mouse transcription factor Pou4f2 with a sea urchin orthologue restores retinal ganglion cell development.

Pou domain transcription factor Pou4f2 is essential for the development of retinal ganglion cells (RGCs) in the vertebrate retina. A distant orthologue of Pou4f2 exists in the genome of the sea urchin (class Echinoidea) Strongylocentrotus purpuratus (SpPou4f1/2), yet the photosensory structure of sea urchins is strikingly different from that of the mammalian retina. Sea urchins have no obvious eyes, but have photoreceptors clustered around their tube feet disc. The mechanisms that are associated with the development and function of photoreception in sea urchins are largely unexplored. As an initial approach to better understand the sea urchin photosensory structure and relate it to the mammalian retina, we asked whether SpPou4f1/2 could support RGC development in the absence of Pou4f2. To answer this question, we replaced genomic Pou4f2 with an SpPou4f1/2 cDNA. In Pou4f2-null mice, retinas expressing SpPou4f1/2 were outwardly identical to those of wild-type mice. SpPou4f1/2 retinas exhibited dark-adapted electroretinogram scotopic threshold responses, indicating functionally active RGCs. During retinal development, SpPou4f1/2 activated RGC-specific genes and in S. purpuratus, SpPou4f2 was expressed in photoreceptor cells of tube feet in a pattern distinct from Opsin4 and Pax6. Our results suggest that SpPou4f1/2 and Pou4f2 share conserved components of a gene network for photosensory development and they maintain their conserved intrinsic functions despite vast morphological differences in mouse and sea urchin photosensory structures.

Animals↗

PubMed2007

FXYD6 is a novel regulator of Na,K-ATPase expressed in the inner ear.

The exquisite sensitivity of the cochlea, which mediates the transduction of sound waves into nerve impulses, depends on the endolymph ionic composition and the endocochlear potential. A key protein in the maintenance of the electrochemical composition of the endolymph is the Na,K-ATPase. In this study, we have looked for the presence in the rat inner ear of members of the FXYD protein family, recently identified as tissue-specific modulators of Na,K-ATPase. Only FXYD6 is detected at the protein level. FXYD6 is expressed in various epithelial cells bordering the endolymph space and in the auditory neurons. FXYD6 co-localizes with Na,K-ATPase in the stria vascularis and can be co-immunoprecipitated with Na,K-ATPase. After expression in Xenopus oocytes, FXYD6 associates with Na,K-ATPase alpha1-beta1 and alpha1-beta2 isozymes, which are preferentially expressed in different regions of the inner ear and also with gastric and non-gastric H,K-ATPases. The apparent K(+) and Na(+) affinities of alpha1-beta1 and alpha1-beta2 isozymes are different. Association of FXYD6 with Na,K-ATPase alpha1-beta1 isozymes slightly decreases their apparent K(+) affinity and significantly decreases their apparent Na(+) affinity. On the other hand, association with alpha1-beta2 isozymes increases their apparent K(+) and Na(+) affinity. The effects of FXYD6 on the apparent Na(+) affinity of Na,K-ATPase and the voltage dependence of its K(+) effect are distinct from other FXYD proteins. In conclusion, this study defines the last FXYD protein of unknown function as a modulator of Na,K-ATPase. Among FXYD protein, FXYD6 is unique in its expression in the inner ear, suggesting a role in endolymph composition.

Amino Acid Sequence↗