Function (Oxford, England)最新文献

{"title":"KATP channels as Target for Remodeling Connectivity in Type 2 Diabetes.","authors":"Fei Kang, Herbert Y Gaisano","doi":"10.1093/function/zqaf013","DOIUrl":"https://doi.org/10.1093/function/zqaf013","url":null,"abstract":"","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143652383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LncRNA GAS5 Regulates Myometrial cells Contractions In a m6A-Dependent Manner.","authors":"Yue Sun, Min Zhang, Tianjun Wang, Shiyun Huang, Qing Zuo, Lanhua Liu, Runrun Feng, Yufei Han, Cen Cao, Haiyan Sun, Yihan Lu, Xinxin Zhu, Yuping Tang, Shuang Wu, Guoqiang Ping, Lizhou Sun, Zhiping Ge, Ziyan Jiang","doi":"10.1093/function/zqaf009","DOIUrl":"https://doi.org/10.1093/function/zqaf009","url":null,"abstract":"<p><strong>Background: </strong>LncRNAs are engaged in signaling pathways in human physiological and pathological states. However, LncRNAs mediate the onset of human labor still remains unknown.</p><p><strong>Methods: </strong>RNA sequencing of lower segment myometrium (in labor vs. not in labor) was analyzed. N6-Methyladenosine (m6A) complexes were detected by RIP and meRIP in human myometrial cells. Plasmid and siRNA transfection was performed, and contraction ability was assessed. RNA pulldown, silver staining, protein mass spectrometry and RIP were used to identify binding proteins. FISH and immunofluorescence costaining were applied to assess the coexpression.</p><p><strong>Results: </strong>GAS5 was upregulated in human myometrium after labor onset. METTL3 and IGF2BP1 maintained GAS5 RNA stability based on actinomycin assay, thus strengthening the contraction of myometrial cells. RIP and meRIP revealed the binding sites of GAS5 with METTL3 and IGF2BP1, respectively. Furthermore, GAS5 binds TPM4 in cytoplasm of myometrium cells and transport TPM4 to the contraction filaments.m6A RNA modifications were also noted in the mouse myometrium after labor onset.</p><p><strong>Conclusion: </strong>These findings highlighted the critical role of m6A modification in GAS5, providing a new method to explore RNA epigenetic regulatory patterns in human paturition.</p>","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143575810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High salt diet increases suprachiasmatic neuronal excitability through endothelin receptor type B signaling.","authors":"Jodi R Paul, Megan K Rhoads, Anna Elam, David M Pollock, Karen L Gamble","doi":"10.1093/function/zqaf014","DOIUrl":"https://doi.org/10.1093/function/zqaf014","url":null,"abstract":"<p><p>Circadian rhythms are 24-hour oscillations in behavioral and biological processes such as blood pressure and sodium excretion. Endothelin receptor B (ETB) has been connected to the molecular clock in peripheral tissues and plays a key role in the regulation of sodium excretion, especially in response to a high salt diet. However, little is known about the role of ETB in the primary circadian pacemaker in the brain, the suprachiasmatic nucleus (SCN), despite recent reports showing its enrichment in SCN astrocytes. In this study, we tested the hypothesis that high salt diet (4.0% NaCl) impacts the circadian system via the ETB receptor at the behavioral, molecular and physiological levels in C57BL/6 mice. Two weeks of high salt diet feeding changed the organization of nighttime wheel-running activity, as well as increased SCN expression of ETB mRNA determined by fluorescence in situ hybridization at night. Neuronal excitability determined using loose-patch electrophysiology was also elevated at night. This high salt diet-induced increase in SCN activity was ameliorated by ex vivo bath application of an ETB antagonist and could be mimicked with acute treatment of endothelin-3. Finally, we found that the excitatory effects of endothelin-3 were blocked with co-application of an NMDA receptor antagonist, suggesting that glutamate mediates endothelin-induced neuronal excitability in the SCN. Together our data demonstrate the presence of functional ETB receptors in SCN astrocytes and point to a novel role for endothelin signaling in mediating neuronal responses to a dietary sodium intake.</p>","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Topical ATP application in the peripheral swallowing-related regions facilitates triggering of the swallowing reflex involving P2×3 receptors.","authors":"Mohammad Zakir Hossain, Hiroshi Ando, Rita Rani Roy, Junichi Kitagawa","doi":"10.1093/function/zqaf010","DOIUrl":"https://doi.org/10.1093/function/zqaf010","url":null,"abstract":"<p><p>The swallowing reflex is a critical component of the digestive process, triggered when food or liquids pass from the oral cavity to the oesophagus. Although adenosine triphosphate (ATP) is involved in various physiological processes, its potential to trigger the swallowing reflex has not been fully explored. This study investigated the ability of ATP to induce the swallowing reflex and examined the involvement of the purinoreceptor P2×3 in this process. We observed that the topical application of exogenous ATP to the superior laryngeal nerve (SLN)-innervated swallowing-related regions dose-dependently facilitated the triggering of the swallowing reflex. P2×3 receptors were predominantly localised on nerve fibres in these regions. Immunoreactivity for P2×3 was observed in intraepithelial and subepithelial nerves, as well as nerves supplying taste-bud-like structures. In the nodose-petrosal-jugular ganglionic complex, P2×3 receptors were present on the cell bodies of approximately 40% of retrogradely traced SLN-afferent neurons. Among these P2×3-immunoreactive SLN-afferent neurons, approximately 59% were medium, 30% were small, and 11% were large. Prior topical application of a P2×3 antagonist in SLN-innervated, swallowing-related regions significantly reduced the number of ATP-induced swallowing reflexes. Furthermore, topical application of a P2×3 receptor agonist more selective than ATP facilitated reflex triggering in a dose-dependent manner. These findings suggest that exogenous ATP facilitates the triggering of the swallowing reflex through the activation of P2×3 receptors. This activation excites afferent neurons that supply peripheral swallowing-related regions, stimulating the swallowing central pattern generator to facilitate the reflex. The current findings suggest the therapeutic potential of ATP or P2×3 agonists for dysphagia treatment and provide valuable physiological insights into the involvement of purinergic signalling in triggering the swallowing reflex.</p>","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Perspective on 'Signal transduction pathway mediating carotid body dependent sympathetic activation and hypertension by chronic intermittent hypoxia'.","authors":"Gary C Sieck","doi":"10.1093/function/zqaf012","DOIUrl":"https://doi.org/10.1093/function/zqaf012","url":null,"abstract":"","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143560177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Does anybody really know what time it is?","authors":"David M Pollock","doi":"10.1093/function/zqaf011","DOIUrl":"https://doi.org/10.1093/function/zqaf011","url":null,"abstract":"","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143560179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phosphatases control the duration and range of cAMP/PKA microdomains.","authors":"Filippo Conca, Doruk Kaan Bayburtlu, Mauro Vismara, Nicoletta C Surdo, Alessandra Tavoni, Leonardo Nogara, Adamo Sarra, Stefano Ciciliot, Giulietta Di Benedetto, Liliana F Iannucci, Konstantinos Lefkimmiatis","doi":"10.1093/function/zqaf007","DOIUrl":"https://doi.org/10.1093/function/zqaf007","url":null,"abstract":"<p><p>The spatiotemporal interplay between the second messenger cyclic AMP (cAMP) and its main effector, Protein kinase A (PKA) is crucial for the pleiotropic nature of this cascade. To maintain a high degree of specificity, the cAMP/PKA axis is organised into functional units called microdomains, precisely distributed within the cell. While the subcellular allocation of PKA is guaranteed by a family of tethers called A-Kinase-anchoring Proteins (AKAPs), the mechanisms underlying the efficient confinement of a microdomain's functional effects are not fully understood. Here we used FRET-based sensors to detect cAMP levels and PKA-dependent phosphorylation within specific subcellular compartments. We find that cellular cAMP levels may depend on different mechanisms and are responsible for the activation of local PKA enzymes. On the other hand, the dephosphorylating actions of phosphatases dictate the duration of the microdomain's effects. To test the range of action of PKA microdomains we used rigid aminoacidic nanorulers to distance our FRET sensors from their original location for 10 or 30 nm. Interestingly, we established that cAMP levels do not affect the spatial range of the microdomain while on the contrary, phosphatase activity provides a functional boundary for phosphorylated PKA targets. Finally, using the same strategy to distance phosphatases from the mitochondria we found that enzymes close to the outer mitochondrial membrane produced a fragmented phenotype that was not observed when phosphatases were moved to 30 nm from the organelle's surface. Our findings contribute to the design of a picture where two microdomain-forming events have distinct roles. Cyclic AMP elevations trigger the initial activation of subcellular PKA moieties, while the temporal and spatial extent of the PKA's actions are regulated by phosphatases.</p>","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"STIMulating Salivary Glands.","authors":"Karla M Márquez-Nogueras, Ivana Y Kuo","doi":"10.1093/function/zqae055","DOIUrl":"10.1093/function/zqae055","url":null,"abstract":"","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11815572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142857105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IK Channel Confers Fine-tuning of Rod Bipolar Cell Excitation and Synaptic Transmission in the Retina.","authors":"Yong Soo Park, Ki-Wug Sung, In-Beom Kim","doi":"10.1093/function/zqae054","DOIUrl":"10.1093/function/zqae054","url":null,"abstract":"<p><p>During retinal visual processing, rod bipolar cells (RBC) transfer scotopic signals from rods to AII amacrine cells as second-order neurons. Elucidation of the RBC's excitation/inhibition is essential for understanding the visual signal transmission. Excitation mechanisms via mGluR6 and voltage-gated Ca2+ channels in the RBCs and GABAergic inhibitory synaptic inputs have been studied in previous studies. However, its intrinsic inhibitory mechanisms like K+ and Cl- channels remain unclear. We focused on RBC's prominent K+ current, which exhibits voltage and Ca2+ dependence. We isolated and confirmed the expression of intermediate-conductance Ca2+-activated K+ channels (IK) in RBCs using the patch-clamp method with IK inhibitors (clotrimazole and TRAM34) and immunohistochemistry. The regulation of the IK channel primarily relies on Ca2+ influx via low-threshold Ca2+ channels during RBC's excitation. Additionally, IK mediates late repolarization and suppresses excessive oscillation of the membrane potential in the RBCs, enabling fast and transient synaptic transmission to AII amacrine cells. Our findings highlight the unique role of the IK channel in RBCs, suggesting that it plays a critical role in the scotopic pathway by fine-tuning RBC activity.</p>","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11815585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Core Circadian Clock Factor, Bmal1, Transduces Sex-specific Differences in Both Rhythmic and Nonrhythmic Gene Expression in the Mouse Heart.","authors":"Xiping Zhang, Spencer B Procopio, Haocheng Ding, Maya G Semel, Elizabeth A Schroder, Mark R Viggars, Tanya S Seward, Ping Du, Kevin Wu, Sidney R Johnson, Abhilash Prabhat, David J Schneider, Isabel G Stumpf, Ezekiel R Rozmus, Zhiguang Huo, Brian P Delisle, Karyn A Esser","doi":"10.1093/function/zqae053","DOIUrl":"10.1093/function/zqae053","url":null,"abstract":"<p><p>It has been well established that cardiovascular diseases exhibit significant differences between sexes in both preclinical models and humans. In addition, there is growing recognition that disrupted circadian rhythms can contribute to the onset and progression of cardiovascular diseases. However, little is known about sex differences between the cardiac circadian clock and circadian transcriptomes in mice. Here, we show that the core clock genes are expressed in common in both sexes, but the cardiac circadian transcriptome is very sex-specific. Hearts from female mice expressed significantly more rhythmically expressed genes (REGs) than male hearts, and the temporal distribution of REGs was distinctly different between sexes. To test the contribution of the circadian clock in sex-specific gene expression in the heart, we knocked out the core circadian clock factor Bmal1 in adult cardiomyocytes. The sex differences in the circadian transcriptomes were significantly diminished with cardiomyocyte-specific loss of Bmal1. Surprisingly, loss of cardiomyocyte Bmal1 also resulted in a roughly 8-fold reduction in the number of all differentially expressed genes between male and female hearts. We highlight sex-specific changes in several cardiac-specific transcription factors, including Gata4, Nkx2-5, and Tbx5. While there is still much to learn, we conclude that cardiomyocyte-specific Bmal1 is vital in conferring sex-specific gene expression in the adult mouse heart.</p>","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11815582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}