Cell calcium最新文献

{"title":"Loss of CALU disrupts intracellular Ca²⁺ homeostasis and triggers apoptosis in glioma cells.","authors":"Lingyun Wu, Tong Wu, Hao Liu, Ruzhen Dai, Yan Zhou, Yifan Xu, Bin Huang","doi":"10.1016/j.ceca.2026.103182","DOIUrl":"https://doi.org/10.1016/j.ceca.2026.103182","url":null,"abstract":"<p><p>Glioma is an aggressive primary tumor of the central nervous system. Calcium (Ca²⁺) signaling between the ER and mitochondria is essential for cell survival and death regulation. Calumenin (CALU), an ER-resident Ca²⁺-binding protein, has been implicated in several cancers, but its role in glioma remains unclear. Public datasets (TCGA, CGGA) were analyzed to assess CALU expression and prognosis. We manipulated CALU through transfection technology and tested its role in Ca²⁺ responses, intracellular Ca²⁺ store-associated fluorescence, and mitochondrial Ca²⁺-associated fluorescence signals by means of Fluo-4, Mag-Fluo-4, and Rhod-2 probes, respectively. Mitochondrial Ca²⁺uptake was further assessed using an isolated mitochondrial Calcium Green-5 N assay. Mitochondrial function was assessed through the detection of MMP and mPTP utilizing JC-1 staining and calcein-AM/cobalt assay. Mitochondrial ROS and total ROS were estimated via mitoSox red staining and DCFH-DA assay. The cell apoptosis was appraised utilizing flow cytometry and TUNEL staining. A xenograft model using U87 glioma cells was established to further explore the role of CALU in vivo. CALU expression was highly expressed in gliomas and correlated with poor survival and mitochondrial Ca²⁺ transport genes. CALU depletion reduced intracellular Ca²⁺ store-associated fluorescence, enhanced store-operated Ca²⁺ entry (SOCE), and induced sustained cytosolic Ca²⁺elevation accompanied by enhanced mitochondrial Ca²⁺-associated fluorescence signals and enhanced mitochondrial Ca²⁺ uptake. These changes were associated with decreased MMP, increased mitochondrial calcein fluorescence, elevated ROS generation, and facilitated apoptosis. In vivo, CALU knockdown reduced tumor growth, increased 4-HNE and cleaved caspase-3 expression and reduced Ki-67 expression, which were partially reversed by NAC treatment. These findings suggest that CALU may contribute to the maintenance of intracellular Ca²⁺ homeostasis in glioma cells. Loss of CALU induces SOCE-associated Ca²⁺dysregulation, mitochondrial dysfunction, and ROS-mediated apoptosis, highlighting CALU as a potential therapeutic target for glioma.</p>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"137 ","pages":"103182"},"PeriodicalIF":4.9,"publicationDate":"2026-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148872932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In memoriam: Irene Schulz-Hofer.","authors":"Ivan Bogeski","doi":"10.1016/j.ceca.2026.103154","DOIUrl":"https://doi.org/10.1016/j.ceca.2026.103154","url":null,"abstract":"","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"136 ","pages":"103154"},"PeriodicalIF":4.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148599354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological modulation of TRPV2 enhances migration and induces Immunoglobulin E (IgE)-independent degranulation of mast cells","authors":"Andrea Leipe,&nbsp;Rick Raudszus,&nbsp;Nicole Urban,&nbsp;Michael Schaefer,&nbsp;Kerstin Hill","doi":"10.1016/j.ceca.2026.103166","DOIUrl":"10.1016/j.ceca.2026.103166","url":null,"abstract":"<div><div>Transient receptor potential vanilloid 2 (TRPV2) is highly expressed in immune cells, including mast cells, yet its functional role in mast cell physiology remains incompletely understood. Given the increasing global prevalence of immune disorders, elucidating TRPV2-mediated mechanisms may uncover novel therapeutic approaches. Using fluorometric Ca²⁺ influx assays and electrophysiological patch-clamp recordings, this study analyzes synergistic effects of the TRPV2 activators AV2–1, cannabidiol and probenecid. Superadditive TRPV2 activation was observed upon co-application of probenecid and cannabidiol, as well as by the combination of AV2–1 and cannabidiol. The effects of the activators were validated in primary mouse bone marrow-derived mast cells (mBMMCs) and the human mast cell-like cell line HMC-1.2. Activation of TRPV2 by the cannabidiol/probenecid combination or by AV2–1 alone induced mBMMC degranulation, as assessed by β-hexosaminidase release, histamine secretion, and increased CD63 surface expression measured by flow cytometry, without evidence of long-term cytotoxicity. TRPV2-dependent degranulation was additive to FcεRI-mediated responses induced by anti-DNP-IgE/DNP-HSA stimulation, indicating mechanistically distinct signaling pathways. In addition, TRPV2 activation enhanced mBMMC migration. All observed effects were abolished by the TRPV2 inhibitor IV2–1 or genetic deletion of TRPV2 in transwell migration assays. These findings demonstrate that pharmacological activation of TRPV2 modulates mast cell effector functions and migration, supporting a role for TRPV2 as an immunomodulatory ion channel and a potential therapeutic target in immune system-related pathologies.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"136 ","pages":"Article 103166"},"PeriodicalIF":4.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148419156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A model for the complete sequence of the human voltage-gated calcium channel (CaV1.2) in a lipid bilayer","authors":"Spencer K. Lile,&nbsp;Caden J. McGarity,&nbsp;Emily M. Campbell,&nbsp;Steven R. Gwaltney,&nbsp;Christopher N. Johnson","doi":"10.1016/j.ceca.2026.103159","DOIUrl":"10.1016/j.ceca.2026.103159","url":null,"abstract":"<div><div>During the past decade, advancements in CryoEM have afforded significant insight into transmembrane regions of ion channels. Portions of cytosolic amino acids have been structurally and biophysically characterized; however, understanding structural relationships and how components integrate into a functional ion channel required clarification. Here, we have calculated an all-atom model for the complete sequence of the cardiac voltage-gated calcium ion channel (Ca_V1.2 alpha-1C and beta-3 subunits) in a lipid bilayer with explicit salt and water. Four one-microsecond molecular dynamics (MD) simulations of the isolated alpha subunit improved backbone torsion angles for non-transmembrane residues relative to the AlphaFold model. Two 500 ns MD simulations of Ca_V1.2 (alpha and beta subunits) provided insight into the binding interface and structural features of the complex. The time component of our MD simulation provided unique insight into side chain dynamics, solvation of voltage sensors, and features of the channel pore. Repeating the alpha subunit simulations with a highly penetrant Timothy Syndrome point mutation (G406R) predicted changes to side chain dynamics that may contribute to a destabilization mechanism of an inactivated channel configuration. Lastly, a comparison of our WT post-MD model with empirical data obtained in the presence of small molecules yielded mechanistic insights into several small molecule Ca_V1.2 interactions.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"136 ","pages":"Article 103159"},"PeriodicalIF":4.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148293394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-throughput quantitation of pathogen-induced calcium signals captured through live-cell fluorescence microscopy","authors":"J. Thomas Gebert,&nbsp;Ethan M. Huleatt,&nbsp;Francesca J. Scribano,&nbsp;Michael R. Eledge,&nbsp;Lauren E. Dorn,&nbsp;Sammy K. Hasmi,&nbsp;Joseph M. Hyser","doi":"10.1016/j.ceca.2026.103160","DOIUrl":"10.1016/j.ceca.2026.103160","url":null,"abstract":"<div><div>Many intracellular pathogens manipulate host cell calcium to facilitate their survival and replication. Live-cell microscopy using fluorescent calcium indicators has become an indispensable tool for characterizing the mechanisms underlying both homeostatic and pathogen-induced cellular calcium dynamics, but such imaging must be coupled with robust quantitative analysis. Further, calcium imaging is most powerful when paired with reductive studies targeting calcium-modulating proteins. The lack of specific inhibitors or agonists to directly target most pathogen-induced calcium signals precludes many of the approaches that have allowed for robust characterization of major eukaryotic cell calcium signaling mechanisms, such as ER Ca²⁺ release by inositol triphosphate receptors. Given this, we sought to develop quantitative imaging pipelines tailored for the characterization of pathogen-induced calcium signals. Using rotavirus as a prototypical calcium-modulating pathogen, we developed and optimized a suite of computational tools for automated quantitation of both intra- and inter-cellular calcium signals detected via live-cell imaging of infected epithelial monolayers expressing genetically encoded calcium indicators. Using recombinant strains of rotavirus that express fluorescent markers, we developed a system that allows for automated detection of rotavirus-infected cells and normalization of signals to infectivity. All tools were built in ImageJ, making them freely available and adaptable across operating systems and microscope setups. These tools required minimal active time from the user and allowed for the extraction of signal parameters previously unquantifiable, increasing the speed and breadth of characterization.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"136 ","pages":"Article 103160"},"PeriodicalIF":4.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148301179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calcium handling properties and arrhythmia vulnerability of cardiomyocytes from dystrophin-deficient mdx mice","authors":"Jakob Sauer,&nbsp;Jessica Marksteiner,&nbsp;Elena Lilliu,&nbsp;Christopher Dostal,&nbsp;Ana Isabel Antunes Goncalves,&nbsp;Attila Kiss,&nbsp;Bruno K. Podesser,&nbsp;Helmut Kubista,&nbsp;Hannes Todt,&nbsp;Xaver Koenig,&nbsp;Karlheinz Hilber","doi":"10.1016/j.ceca.2026.103162","DOIUrl":"10.1016/j.ceca.2026.103162","url":null,"abstract":"<div><div>Cardiomyopathy and arrhythmia development significantly contribute to mortality in patients with Duchenne muscular dystrophy (DMD), a fatal muscle disorder caused by dystrophin deficiency. Previous studies suggested that abnormal Ca handling is an important causative factor for cardiac involvement in DMD. Here, we aimed to provide an extensive analysis of Ca handling properties and arrhythmia vulnerability of cardiomyocytes from the dystrophin-deficient mdx mouse, the most common DMD animal model. Whole cell patch clamp experiments showed that currents through L-type Ca channels are similar in wild-type and mdx cardiac Purkinje myocytes. Intracellular Ca measurements revealed that the decay of electrically evoked Ca transients is significantly prolonged in mdx compared to wild-type ventricular cardiomyocytes, thereby suggesting slowed Ca removal from the cytosol by the sarcoplasmic/endoplasmic reticulum Ca ATPase. The diastolic sarcoplasmic reticulum Ca leak and the resting concentration of free Ca in the cytosol were not significantly increased in mdx compared to wild-type ventricular cardiomyocytes. The occurrence of arrhythmogenic delayed afterdepolarizations (DADs), which are provoked by dysregulated Ca handling, was also not enhanced in mdx compared to wild-type ventricular cardiomyocytes. In conclusion, this work provides evidence that the only significant Ca handling abnormality in mdx cardiomyocytes is slowed removal of cytosolic Ca after release from the sarcoplasmic reticulum. Since the susceptibility of mdx ventricular cardiomyocytes to DADs was normal, cardiac arrhythmias in mdx mice might primarily be triggered by other arrhythmogenic mechanisms than DADs.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"136 ","pages":"Article 103162"},"PeriodicalIF":4.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148338105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatially multiplexed stimulation reveals nonlinear calcium signaling in platelets","authors":"Mikhail A. Panfilov,&nbsp;Alexey Yu. Vorob’ev,&nbsp;Olga Yu. Selyutina,&nbsp;Andrey Yu. Komarovskikh,&nbsp;Nikolay E. Polyakov,&nbsp;Alexander Moskalensky","doi":"10.1016/j.ceca.2026.103165","DOIUrl":"10.1016/j.ceca.2026.103165","url":null,"abstract":"<div><div>Platelet activation arises from the integration of multiple biochemical cues, but how platelets respond to spatially heterogeneous combinations of agonists and inhibitors remains poorly understood. Here we applied spatially multiplexed stimulation using two independently controlled light-sensitive compounds to generate localized regions enriched in ADP, epinephrine, or nitric oxide, as well as their combinations. Calcium imaging of platelet populations revealed that different spatial contexts produced qualitatively distinct activation dynamics. In regions with high ADP, responses were robust and were selectively suppressed by nitric oxide, whereas epinephrine had little additional effect. In regions with low ADP, epinephrine enhanced calcium signals, indicating increased sensitivity to weak stimulation. A distinct activation mode emerged when low ADP was combined with both epinephrine and nitric oxide: platelets exhibited delayed yet sustained calcium elevations, suggesting nonlinear integration of sensitizing and inhibitory inputs. These results show that spatial variation in multiple stimuli can give rise to diverse platelet activation patterns, highlighting the importance of local agonist composition in shaping platelet signaling dynamics.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"136 ","pages":"Article 103165"},"PeriodicalIF":4.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148387413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular actors of the Calcium signaling in the endothelial-to-mesenchymal transition: poorly explored therapeutic targets","authors":"Romain Guinamard,&nbsp;Corentin Kerevel,&nbsp;Anaïs Darengosse,&nbsp;Valentin Platel,&nbsp;Laurent Sallé,&nbsp;Christophe Simard","doi":"10.1016/j.ceca.2026.103163","DOIUrl":"10.1016/j.ceca.2026.103163","url":null,"abstract":"<div><div>Endothelial-to-mesenchymal transition (EndMT) is a cell trans-differentiation process which occurs during embryonic development as well as in a variety of pathological contexts. During this process, cells lose their endothelial lineage markers and gain mesenchymal ones. It is stimulated by several factors, such as TGF-β, high glucose, or hypoxia, which trigger intracellular pathways, mainly the Smad and ERK pathways, leading to modulation of transcription factors. While Ca²⁺ signaling is known to participate in a wide variety of cellular processes, its role in the context of EndMT is only partially understood, although several Ca²⁺-carrying and Ca²⁺-regulated proteins have been shown to influence EndMT. These include Ca²⁺-permeable channels from the mechanosensitive Piezo family and members of the TRP family; the actors involved in store-operated Ca²⁺ entry, including IP₃-receptors located on the endoplasmic reticulum membrane, the endoplasmic reticulum Ca²⁺ sensor STIM1, and the Ca²⁺-permeable plasma membrane channel Orai1; the mitochondrial Ca²⁺uniporter complex; Ca²⁺-activated channels such as the non-selective monovalent cation channel TRPM4 and the big-conductance K⁺ channel BK_Ca; Ca²⁺-regulated signaling pathways such as the Ca²⁺-calmodulin-calcineurin-NFAT pathway and the calpain-ERK pathway.</div><div>After a brief description of Ca²⁺ signaling in endothelial cells, this review will specifically detail the available data on the Ca²⁺ signaling in EndMT. Links between Ca²⁺ signaling and other signaling pathways leading to EndMT will be discussed. Finally, molecular targets that may be valuable to explore in order to prevent EndMT will be highlighted.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"136 ","pages":"Article 103163"},"PeriodicalIF":4.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148327060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calorie restriction modulates beta cell IP3R activity to regulate Ca2+ homeostasis and cell network connectivity","authors":"Johannes Pfabe,&nbsp;Amanda Cambraia,&nbsp;Prasanna K Dadi,&nbsp;Melanie Cutler,&nbsp;Cristiane dos Santos,&nbsp;Christopher Acree,&nbsp;Aliyah Habashy,&nbsp;Guy Perkins,&nbsp;Mark H Ellisman,&nbsp;David A. Jacobson,&nbsp;Marjan Slak Rupnik,&nbsp;Rafael Arrojo e Drigo","doi":"10.1016/j.ceca.2026.103161","DOIUrl":"10.1016/j.ceca.2026.103161","url":null,"abstract":"<div><div>Calorie restriction (CR) promotes beta cell longevity by regulating cell identity, organelle and protein homeostasis, and metabolism pathways. CR beta cells have higher cAMP levels and mitochondria with an elevated potential to generate ATP. However, CR beta cells have reduced insulin secretion due to increased peripheral insulin sensitivity. How CR impacts beta cell Ca²⁺ homeostasis to regulate beta cell insulin release remains unknown. We investigated this question using acute pancreatic tissue slices prepared from ad-libitum (AL) or CR mice loaded with a low affinity Ca²⁺ indicator and recorded cytosolic Ca²⁺ gradients with fast confocal imaging. We exposed these slices to increasing glucose concentrations and applied our semi-automatic analysis pipeline to detect thousands of individual beta cells followed by identification of individual Ca²⁺ spiking events. We observed that elevated cAMP in CR beta cells causes fast short-amplitude Ca²⁺ oscillations that potentiate insulin release despite a largely disconnected beta cell network landscape. Using acetylcholine stimulation, we found that faster IP₃R-driven Ca²⁺ oscillations linked to higher cytosolic cAMP levels protect beta cells against acute depletion of ER Ca²⁺. Therefore, this study demonstrates that CR promotes beta cell cAMP and ER Ca²⁺ homeostasis to enhance beta cell secretory function.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"136 ","pages":"Article 103161"},"PeriodicalIF":4.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148396047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Store operated Ca2+ entry in neural crest cells and their derivatives","authors":"Olivier Romito,&nbsp;Nicolas R. Chevalier","doi":"10.1016/j.ceca.2026.103168","DOIUrl":"10.1016/j.ceca.2026.103168","url":null,"abstract":"<div><div>Neural crest cells (NCCs) are multipotent stem cells that migrate extensively during embryogenesis and give rise to a broad spectrum of derivatives, including melanocytes, Schwann cells, chromaffin cells, and neurons of the enteric nervous system. NCC proliferation, migration, or differentiation defects lead to a group of disorders collectively known as neurocristopathies. Understanding the signaling pathways that govern NCC behavior is therefore crucial for elucidating the origins of these conditions. Store-Operated Calcium Entry (SOCE) is recognized as the principal calcium influx mechanism in non-excitable cells and regulates key cellular processes such as proliferation, migration, and differentiation. Accumulating evidence indicates a significant role for Ca²⁺ signaling and SOCE in multiple NCC-derived cell types. This review examines current knowledge on Ca²⁺ signaling mediated by SOCE in NCCs and their derivatives, and discusses how dysregulated SOCE signaling may influence the pathogenesis of neurocristopathies.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"136 ","pages":"Article 103168"},"PeriodicalIF":4.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148410496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}