Cell calcium最新文献

{"title":"Campari2 genomic interrogation of homeostatic calcium activity identifies TIM1 as a negative regulator of T cell function","authors":"Sana Kouba ,&nbsp;Xin Zhang ,&nbsp;Raphael Néré,&nbsp;Cyril Castelbou,&nbsp;Nicolas Demaurex,&nbsp;Amado Carreras-Sureda","doi":"10.1016/j.ceca.2025.103036","DOIUrl":"10.1016/j.ceca.2025.103036","url":null,"abstract":"<div><div>Calcium signals regulate crucial cellular functions yet many genes coding for Ca²⁺handling proteins remain unknown as their identification relies on low-throughput single-cell approaches. Here we describe a method to measure Ca²⁺ activity using CaMPARI2, flow cytometry and pooled genome interrogation. CAMPARI2 screen (CaMP-Screen) identified enhancers and inhibitors of homeostatic Ca²⁺ activity, highlighting a predominant role for store-operated Ca²⁺ entry (SOCE) and lipid signalling pathways. Genes reducing basal Ca²⁺ activity were linked to Prader Willy syndrome, T cell dysfunction, and deafness. Silencing of <em>HAVCR1</em> gene, coding for T cell transmembrane immunoglobulin and mucin (TIM1), enhanced Ca²⁺ signals in T cells and promoted signaling under resting but not after TCR engagement. Our findings establish CaMP-Screen as an efficient detector of low-amplitude Ca²⁺ signals and identify new genes associated to pathologies that regulate Ca²⁺ homeostasis, reporting TIM1 as a negative regulator of Ca²⁺ signals driving T cell function.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"129 ","pages":"Article 103036"},"PeriodicalIF":4.3,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144123993","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":"The role of SERCA in vascular diseases, a potential therapeutic target","authors":"Qinghua Yu,&nbsp;Wen Tian","doi":"10.1016/j.ceca.2025.103039","DOIUrl":"10.1016/j.ceca.2025.103039","url":null,"abstract":"<div><div>SERCA, the sarco/endoplasmic reticulum Ca²⁺-ATPase, is a pivotal protein that transports calcium ions (Ca²⁺) from the cytoplasm into the sarcoplasmic/endoplasmic reticulum (SR/ER), thus sustaining cellular Ca²⁺ homeostasis. A growing body of evidence indicates that SERCA dysfunction correlates with disrupted cellular Ca²⁺ homeostasis and ER stress, precipitating a spectrum of chronic diseases. As a regulator of Ca²⁺ homeostasis, SERCA emerges as a potential therapeutic target for conditions associated with Ca²⁺ imbalance. This review delineates the association between SERCA and a variety of vascular diseases.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"129 ","pages":"Article 103039"},"PeriodicalIF":4.3,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143942638","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":"Stable expression of SARS-CoV-2 envelope viroporin promotes intracellular calcium depletion in human cells: relevance for endoplasmic reticulum stress, cell proliferation, pluripotency and lineage differentiation","authors":"Cesare Sala ,&nbsp;Andrea Ninu ,&nbsp;Valentina Balducci ,&nbsp;Giada Allegro ,&nbsp;Alberto Montalbano ,&nbsp;Matteo Lulli ,&nbsp;Martina Lucia Boccitto ,&nbsp;Elena Guzzolino ,&nbsp;Valentina Spinelli ,&nbsp;Annarosa Arcangeli ,&nbsp;Laura Sartiani ,&nbsp;Elisabetta Cerbai","doi":"10.1016/j.ceca.2025.103032","DOIUrl":"10.1016/j.ceca.2025.103032","url":null,"abstract":"<div><div>SARS-CoV-2 infection affects the respiratory system but also many tissues and organs that may be adversely compromised. Accordingly, recent evidence has assessed virus ability to infect different cell phenotypes, translate viral proteins and promote virus replication. Among them, Envelope (E) proteins sustain virus replication, promote inflammatory processes and remodelling of host cells. However, despite advances on structure and sequence, E-protein specific location and effects in human host cells are still controversial and poorly investigated.</div><div>Using lentiviral vectors, we established HEK293 and hiPS cell lines stably expressing E-protein. Immunocytochemistry showed E-protein mainly locates within the endoplasmic reticulum, the ERGIC and the Golgi compartments, while only HEK293 cells display some protein staining in cell periphery suggesting a possible insertion into the plasmalemma. Electrophysiological recordings in HEK293 cells revealed E-protein self-assembles in the plasma membrane to mediate a cation efflux pore that is sensitive to amantadine blockade. Calcium fluorescence imaging in HEK293 and hiPS cells demonstrated E-protein expression induces a marked depletion of thapsigargin-sensitive intracellular calcium stores. The altered calcium homeostasis associates to reduced cell metabolic activity, mitochondrial potential, proliferation rate and promotes ER stress. Finally, trilineage differentiation of hiPS cells indicated E-protein expression preserves cell pluripotency while selectively impairs mesodermal differentiation. These results unveil a critical role of stable E-viroporin expression that through alteration of ER Ca²⁺ homeostasis, metabolic activity and induction of ER stress affects important cellular functions, including the differentiative process from pluripotent to mesodermal progenitors, a critical cell population in self-repair and homeostasis of most human tissue and organs.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"128 ","pages":"Article 103032"},"PeriodicalIF":4.3,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143869415","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":"The role of ion channels in the regulation of dendritic cell function","authors":"Shi-Li Zhou ,&nbsp;Lan-Lan Zhong ,&nbsp;Yi-Lan Wu ,&nbsp;Si-Wen Ji ,&nbsp;Yong Li ,&nbsp;Na Niu","doi":"10.1016/j.ceca.2025.103031","DOIUrl":"10.1016/j.ceca.2025.103031","url":null,"abstract":"<div><div>Ion channels, membrane proteins that facilitate the transport of various inorganic ions across hydrophobic cellular lipid membranes, are ubiquitous in a wide variety of cell and tissue types. They are involved in establishing the cell membrane potential and play a role in various physiological activities by regulating ion concentrations within the cell. Dendritic cells (DCs) are specialised antigen-presenting cells found mainly on the surface of the body (skin and mucous membranes), in the mesenchyme of most organs, in the T-cell compartment of the spleen and in lymph nodes. DCs exert an important influence on the regulation of inflammation by activating T cells and producing cytokines. Studies have shown that ion channels expressed in DCs contribute to the regulation of the immune response, making them a key component of the immune system. This review summarises the major scientific advances in understanding the functional impact of ion channels (calcium channels, sodium channels and aquaporin) in DCs, including the regulation of inflammatory responses, antigen presentation, maturation, migration and cytokine production, to inform ongoing studies of ion channel function in DCs.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"128 ","pages":"Article 103031"},"PeriodicalIF":4.3,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848346","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":"Calcium acts as a critical determinant of mitochondria-nuclear networking driven retrograde signaling","authors":"Kriti Ahuja,&nbsp;Rajender K. Motiani","doi":"10.1016/j.ceca.2025.103017","DOIUrl":"10.1016/j.ceca.2025.103017","url":null,"abstract":"<div><div>Mitochondria are robust signaling organelle that regulate a variety of cellular functions. One of the key mechanisms that drive mitochondrial signaling is inter-organelle crosstalk. Mitochondria communicates with other organelles primarily via exchange of calcium (Ca²⁺), reactive oxygen species (ROS) and lipids across organelle membranes. Mitochondria has its own genome but a majority of mitochondrial proteins are encoded by nuclear genome. Therefore, several mitochondrial functions are controlled by nucleus via anterograde signaling. However, the role of mitochondria in driving expression of genes encoded by nuclear genome has recently gained attention. Recent studies from independent groups have demonstrated a critical role for mitochondrial Ca²⁺signaling in stimulating nuclear gene expression. These studies report that inhibition of mitochondrial Ca²⁺uptake through silencing of Mitochondrial Ca²⁺Uniporter (MCU) leads to Ca²⁺oscillations in the cytosol. The rise in cytosolic Ca²⁺ results in activation of Ca²⁺ sensitive transcription factors such as NFATs and NF-<span><math><mi>κ</mi></math></span>B. These transcription factors consequently induce expression of their target genes in the nuclear genome. It is important to highlight that these groups used different cell types and elegantly presented a phenomenon that is conserved across various systems. Notably, mitochondrial Ca²⁺ signaling mediated transcriptional regulation controls diverse cellular functions ranging from B-cell activation, melanogenesis and aging associated inflammation. Future studies on this signaling module would result in better understanding of this axis in human pathophysiology and could lead to development of novel therapeutic strategies.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"127 ","pages":"Article 103017"},"PeriodicalIF":4.3,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143839191","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":"Scaling up neuronal Ca2+, signaling on ER ladders","authors":"Khaled Machaca","doi":"10.1016/j.ceca.2025.103016","DOIUrl":"10.1016/j.ceca.2025.103016","url":null,"abstract":"<div><div>Dendritic Ca²⁺ signaling is critical for neural transmission and signal processing, however the detailed molecular mechanisms have not been elucidated. Using elegant and complementary imaging approaches Benedetti et al. discover a distinctive ER ladder architecture in dendrites and show that precise localization of Ca²⁺ signaling proteins at endoplasmic reticulum (ER)-plasma membrane (PM) junctions supports integration of Ca²⁺ signaling along the dendrite.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"127 ","pages":"Article 103016"},"PeriodicalIF":4.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143799197","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":"H2S treatment reverts cardiac hypertrophy and increases SERCA2a activity but does not fully restore cardiac Ca2+ handling in hypertensive rats","authors":"Grecia J. Medina-Terol ,&nbsp;Luis Chimal ,&nbsp;Saúl Huerta de la Cruz ,&nbsp;Guillermo Ávila ,&nbsp;Alberto Aranda ,&nbsp;David Cruz-Robles ,&nbsp;David Centurión ,&nbsp;Julio Altamirano ,&nbsp;Rocio Rojo ,&nbsp;Norma Leticia Gómez-Viquez","doi":"10.1016/j.ceca.2025.103015","DOIUrl":"10.1016/j.ceca.2025.103015","url":null,"abstract":"<div><div>Hydrogen sulfide (H₂S) has been proposed to play a cardioprotective role, particularly due to its ability to revert left ventricular hypertrophy (LVH) and mitigate cardiac dysfunction in various cardiomyopathies, including hypertensive heart disease. However, the extent to which cardioprotection by H₂S involves improvement in Ca²⁺ handling remains unclear. Although H₂S has been reported to influence the function of key Ca²⁺ handling proteins, most studies have focused on acute administration of H₂S donors in isolated cardiomyocytes, rather than in a therapeutic context. In this study, we used a rat model of hypertension induced by abdominal aortic coarctation (AAC) to evaluate the therapeutic potential of NaHS, an H₂S donor, on LVH and Ca²⁺ handling. After 8 weeks of AAC, hypertensive rats developed moderate LVH, which was accompanied by a reduction in both the amplitude and the rate of rise of systolic Ca²⁺ transients, as well as a decrease in sarcoplasmic reticulum (SR) Ca²⁺ load. Despite the reduced SR Ca²⁺ load, the frequency of diastolic Ca²⁺ sparks remained high, while the incidence and propagation rate of spontaneous Ca²⁺ waves significantly increased, suggesting enhanced diastolic SR Ca²⁺ leak, most likely due to hypersensitivity of ryanodine receptors (RyR2) to Ca²⁺. On the other hand, NaHS administration during the final 4 weeks of AAC reverted both LVH and hypertension, and increased SR Ca²⁺ reuptake mediated by the SR Ca²⁺ ATPase (SERCA2a). However, NaHS treatment failed to restore the amplitude and rate of rise of systolic Ca²⁺ transients or SR Ca²⁺ load. Furthermore, SR Ca²⁺ leak might have worsened, since spontaneous Ca²⁺ waves increased. In conclusion, NaHS treatment does not appear to normalize all Ca²⁺ handling properties during hypertensive LVH. On the contrary, NaHS may exert an arrhythmogenic effect, likely due to enhanced SERCA2a activity under conditions of unresolved RyR2 Ca²⁺ hypersensitivity.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"128 ","pages":"Article 103015"},"PeriodicalIF":4.3,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143769152","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":"Crosstalk between calcium and reactive oxygen species signaling in cancer revisited","authors":"Trayambak Pathak ,&nbsp;J.Cory Benson ,&nbsp;Priscilla W. Tang ,&nbsp;Mohamed Trebak ,&nbsp;Nadine Hempel","doi":"10.1016/j.ceca.2025.103014","DOIUrl":"10.1016/j.ceca.2025.103014","url":null,"abstract":"<div><div>The homeostasis of cellular reactive oxygen species (ROS) and calcium (Ca²⁺) are intricately linked. ROS signaling and Ca²⁺ signaling are reciprocally regulated within cellular microdomains and are crucial for transcription, metabolism and cell function. Tumor cells often highjack ROS and Ca²⁺ signaling mechanisms to ensure optimal cell survival and tumor progression. Expression and regulation of Ca²⁺ channels and transporters at the plasma membrane, endoplasmic reticulum, mitochondria and other endomembranes are often altered in tumor cells, and this includes their regulation by ROS and reactive nitrogen species (RNS). Likewise, alterations in cellular Ca²⁺ levels influence the generation and scavenging of oxidants and thus can alter the redox homeostasis of the cell. This interplay can be either beneficial or detrimental to the cell depending on the localization, duration and levels of ROS and Ca²⁺ signals. At one end of the spectrum, Ca²⁺ and ROS/RNS can function as signaling modules while at the other end, lethal surges in these species are associated with cell death. Here, we highlight the interplay between Ca²⁺ and ROS in cancer progression, emphasize the impact of redox regulation on Ca²⁺ transport mechanisms, and describe how Ca²⁺ signaling pathways, in turn, can regulate the cellular redox environment.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"127 ","pages":"Article 103014"},"PeriodicalIF":4.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143686353","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":"Mitochondrial dysfunction and carcinogenesis: The engagement of ion channels in cancer development","authors":"Gilnei Bruno da Silva ,&nbsp;Geórgia de Carvalho Braga ,&nbsp;Júlia Leão Batista Simões ,&nbsp;Margarete Dulce Bagatini ,&nbsp;Aniela Pinto Kempka","doi":"10.1016/j.ceca.2025.103010","DOIUrl":"10.1016/j.ceca.2025.103010","url":null,"abstract":"<div><div>Mitochondria represent a fundamental structure for cellular homeostasis, controlling multiple conditions regarding energetic functions and cellular survival. To maintain these organelles functioning in ideal conditions, their membranes count with ion channels for different inorganic ions, which must be balanced to offer the proper function for both the organelle and the cell. However, studies have shown that other health conditions impair the activities of mitochondrial ion channels, including cancer. In this sense, the altered activities of potassium, calcium, and calcium-activated potassium channels are mainly linked with cancer development and cellular homeostasis alteration, demonstrating their role as pharmacological targets. With that in mind, scientists have found significant mitochondrial and cellular responses related to apoptosis and reduction of cellular survival from cells with modulated ion channels, indicating the potential of this possible therapy in carcinogenic contexts. Nonetheless, few studies still evaluate mitochondrial ion channel modulation as a treatment against cancer. Hence, more research must be conducted on this subject.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"128 ","pages":"Article 103010"},"PeriodicalIF":4.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143552733","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":"Mitochondrial Ca2+ uniporter b (MCUb) regulates neuronal Ca2+ dynamics and resistance to ischemic stroke","authors":"Tam Nguyen ,&nbsp;Zhihong Lin ,&nbsp;Nirav Dhanesha ,&nbsp;Rakesh B. Patel ,&nbsp;Mallorie Lane ,&nbsp;Grant C. Walters ,&nbsp;Leonid P. Shutov ,&nbsp;Stefan Strack ,&nbsp;Anil K. Chauhan ,&nbsp;Yuriy M. Usachev","doi":"10.1016/j.ceca.2025.103013","DOIUrl":"10.1016/j.ceca.2025.103013","url":null,"abstract":"<div><div>Mitochondrial Ca²⁺ transport regulates many neuronal functions including synaptic transmission, ATP production, gene expression and neuronal survival. The mitochondrial Ca²⁺ uniporter (MCU) is the core molecular component of the mitochondrial Ca²⁺ uptake complex in the inner mitochondrial membrane. MCUb is a paralog of MCU that negatively regulates mitochondrial Ca²⁺ uptake in the heart and the cells of the immune system. However, the function of MCUb in the brain is largely unknown. Here, we report that MCUb knockout (KO) led to enhanced mitochondrial Ca²⁺ uptake in cortical neurons. By simultaneously monitoring changes in cytosolic and mitochondrial Ca²⁺ concentrations, [Ca²⁺]_cyt and [Ca²⁺]_mt, respectively, we also found that MCUb KO reduced the [Ca²⁺]_cyt threshold required to induce mitochondrial uptake in cortical neurons during electrical stimulation. Exposure of cortical neurons to toxic concentrations of glutamate led to a collapse of mitochondrial membrane potential (ΔΨ_mt) and [Ca²⁺]_cyt deregulation, and MCUb deletion accelerated the development of both events. Furthermore, using the middle cerebral artery occlusion (MCAO) as a model of transient ischemic stroke in mice, we found that MCUb KO significantly increased MCAO-induced brain damage in male, but not female mice. These results suggest that MCUb regulates neuronal Ca²⁺ dynamics and excitotoxicity and reveal a sex-dependent role of MCUb in controlling resistance to brain damage following ischemic stroke.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"128 ","pages":"Article 103013"},"PeriodicalIF":4.3,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578745","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}