Cell calcium最新文献

{"title":"Calcium imaging: Unraveling the neurobiological mechanisms of depression across cellular and circuit dimensions","authors":"Xu Han ,&nbsp;Jinfang Song ,&nbsp;Zihui Geng ,&nbsp;Runxin Li ,&nbsp;Bingjin Li","doi":"10.1016/j.ceca.2025.103054","DOIUrl":"10.1016/j.ceca.2025.103054","url":null,"abstract":"<div><div>Calcium imaging has emerged as a pivotal technique for monitoring neuronal and glial activity, gaining widespread recognition in neuroscience research. This method primarily utilizes genetically encoded calcium indicators (GECIs) or synthetic fluorescent dyes to detect physiologically relevant calcium dynamics. Despite being one of the most prevalent mental disorders, depression's pathogenesis remains poorly understood. Calcium imaging serves as a powerful tool to identify depression-related cell types and neural circuits. This review systematically summarizes the evolution of calcium indicators and their integration with behavioral paradigms, electrophysiology, optogenetics, and chemogenetics to elucidate cellular and circuit mechanisms underlying depression. In addition, calcium imaging in depression and other disease comorbidities is also discussed. These synthesized findings establish a framework for developing precision-targeted antidepressant interventions.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"130 ","pages":"Article 103054"},"PeriodicalIF":4.3,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144596591","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":"Dietary calcium intake controls epithelial expression of TRPV6 independent of 1,25(OH)2D3 endocrine signaling","authors":"Hinata Tanishige ,&nbsp;Atsushi Uekawa ,&nbsp;Hitoki Yamanaka ,&nbsp;Shigeaki Kato ,&nbsp;Ritsuko Masuyama","doi":"10.1016/j.ceca.2025.103053","DOIUrl":"10.1016/j.ceca.2025.103053","url":null,"abstract":"<div><div>Dietary calcium intake modifies the action of active vitamin D [1,25(OH)₂D₃], which promotes the expression of transient receptor potential vanilloid (TRPV) 6, an epithelial calcium channel, to initiate intestinal calcium absorption in response to biological requirements. However, it is unclear whether the change caused by dietary intake results from endocrine regulation or the direct responses to luminal contents. In this study, to reveal the underlying mechanisms of intestinal calcium transport in response to dietary intake, we assessed the early postprandial responses in mice.</div><div>Although mice lacking intestinal vitamin D receptor function (<em>Int Vdr-</em>) exhibited severe calcium deficiency, a high-calcium diet (1 % calcium) containing 2-fold calcium compared to a control diet reversed impaired calcium absorption and compensated for the mechanisms of 1,25(OH)₂D₃-dependent transcellular calcium transport. Additionally, the calcium-sensing receptor (CaSR) was abundantly present at the basolateral site in the intestine and the signals were emphasized by a high-calcium diet.</div><div>To examine the direct response of intestinal epithelium to dietary intake, wild-type (<em>Int Vdr+</em>) and <em>Int Vdr-</em> mice were fed a control or high-calcium diet for 30- or 60-min after 23 h fasting. Serum glucose levels increased 30 min post-feeding in either genotype. TRPV6 expression increased 30 min post-feeding, whereas serum calcium levels were unaltered, suggesting that dietary intake stimulates TRPV6 expression.</div><div>These data suggest that the regulation of calcium absorption activated immediately after feeding differs from the mechanism involving endocrine responses. Factors altered in the early phase of feeding, such as glucose, may contribute to the regulation of calcium absorption.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"130 ","pages":"Article 103053"},"PeriodicalIF":4.3,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144665828","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":"Macrophage migration inhibitory factor induces phospholamban phosphorylation in cardiac muscle","authors":"Zihan Tang ,&nbsp;Feng Liu ,&nbsp;Miyuki Nishi ,&nbsp;Fabienne Mackay ,&nbsp;Mutsuo Harada ,&nbsp;Hiroshi Takeshima","doi":"10.1016/j.ceca.2025.103051","DOIUrl":"10.1016/j.ceca.2025.103051","url":null,"abstract":"<div><div>The pleiotropic cytokine macrophage migration inhibitory factor (MIF) elevates sarcoplasmic reticulum (SR) Ca²⁺ content and enhances Ca²⁺ transient in cardiac muscle. Our imaging and immunoblot data indicated that the MIF-evoked effect is caused mainly by the phosphorylation of the SR Ca²⁺-pump regulator phospholamban (PLN). Gene expression data suggested that the cluster of differentiation 74 (CD74) and the C-X-C motif chemokine receptor 7 (CXCR7) form a major MIF receptor complex in cardiomyocytes, but CXCR7 activation alone seemed sufficient to exert the MIF-evoked effect. Our pharmacological assessments suggested that phosphoinositide 3-kinase (PI3K), AKT kinase and endothelial nitric oxide synthase (eNOS) were continuously stimulated in the downstream of CXCR7 activation. Furthermore, NO thus generated likely reacted to activate Ca²⁺/calmodulin-dependent protein kinase II (CaMKII), leading to PLN phosphorylation and subsequent SR Ca²⁺-pump activation. Therefore, the CXCR7-PI3K-AKT-eNOS-CaMKII-PLN axis is proposed as a central pathway for MIF-evoked potentiation of cardiac Ca²⁺ signaling.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"130 ","pages":"Article 103051"},"PeriodicalIF":4.3,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144654931","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":"VDAC1 as Janus in cell death and survival: Annexin A5 to the rescue","authors":"Ophélie Champion ,&nbsp;Jacek J. Litewka ,&nbsp;Pawel E. Ferdek ,&nbsp;Geert Bultynck","doi":"10.1016/j.ceca.2025.103052","DOIUrl":"10.1016/j.ceca.2025.103052","url":null,"abstract":"<div><div>VDAC1, a large conductance channel in the outer mitochondrial membrane, plays a crucial role in mitochondrial physiology. VDAC1 supports cellular metabolism and survival by serving as a mitochondrial Ca²⁺-uptake and ATP-exit system. Conversely, VDAC1 also contributes to apoptosis by forming oligomeric pores mediating cytochrome c release. Recently, Oflaz et al., EMBO J, 2025, identified the Ca²⁺-binding protein Annexin A5 as a dynamic, Ca²⁺-dependent switch that enhances VDAC1’s Ca²⁺-transport function while at the same time preventing pro-apoptotic VDAC1 oligomer formation.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"130 ","pages":"Article 103052"},"PeriodicalIF":4.3,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572386","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":"Abnormal calcium activity and CREB phosphorylation are associated with motor memory impairment in presenilin-1 mutant knock-in mice","authors":"Yuan Lin ,&nbsp;Yang Bai ,&nbsp;Alejandro Martin-Avila ,&nbsp;Wei Li ,&nbsp;Xujun Wu ,&nbsp;Edward Ziff ,&nbsp;Wen-Biao Gan","doi":"10.1016/j.ceca.2025.103048","DOIUrl":"10.1016/j.ceca.2025.103048","url":null,"abstract":"<div><h3>Introduction</h3><div>Presenilin (PS) gene mutations cause memory impairment in early-onset familial Alzheimer’s disease (FAD), but the underlying mechanisms remain unclear.</div></div><div><h3>Methods</h3><div>We examined the effects of the PS1 M146V FAD mutation on motor learning, motor learning-related changes in neuronal Ca²⁺activity and CREB phosphorylation in the primary motor cortex.</div></div><div><h3>Results</h3><div>We found that PS1 M146V knock-in mice displayed long-term deficiencies in motor skill learning. Ca²⁺ levels are altered in a cortical layer and neuron type-specific manner in PS1 mutant mice as compared to WT control mice. Notably, while running caused a significant increase of CREB phosphorylation in WT mice, it led to a significant decrease of CREB phosphorylation in layer 5 neurons of mutant mice.</div></div><div><h3>Discussion</h3><div>These findings suggest that alterations of Ca²⁺ activity and CREB phosphorylation in deep cortical layers are early events leading to memory impairment in the PS1 mutation-related familial form of AD.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"130 ","pages":"Article 103048"},"PeriodicalIF":4.3,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144522865","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":"GAT3-dependent regulation of glioma invasiveness via a lipid raft-associated PMCA4 Ca2+ transporter and a downstream CaMKII/CREB signaling – implications for compartmentalized signaling in glioma tumors","authors":"Marta Sobolczyk-Prawda ,&nbsp;Agnieszka Kapsa ,&nbsp;Malwina Lisek ,&nbsp;Julia Tomczak ,&nbsp;Katarzyna Sobierajska ,&nbsp;Maciej Radek ,&nbsp;Feng Guo ,&nbsp;Tomasz Boczek","doi":"10.1016/j.ceca.2025.103050","DOIUrl":"10.1016/j.ceca.2025.103050","url":null,"abstract":"<div><div>Emerging evidence underscores the crucial role of compartmentalized Ca²⁺ and GABA signaling in the development and progression of gliomas. Our findings reveal that low GAT3 expression and high PMCA4 levels are strongly associated with poor survival outcomes in glioma patients, suggesting their involvement in tumor progression. Using C6 glioma model, we uncovered a dynamic interaction between GAT3 and PMCA4 within lipid raft microdomains, which plays a key role in fine-tuning of localized Ca²⁺ dynamics in response to GABA stimulation. Knockdown of PMCA4 increased resting Ca²⁺concentration and enhanced Ca²⁺ accumulation in lipid rafts following 3-min pulse GABA stimulation, significantly impairing glioma cell migration and invasion. Interestingly, the expression of Ca²⁺ chelator parvalbumin in rafts abolished both baseline and GABA-stimulated Ca²⁺ rises, effectively restoring the migratory and invasive potential of tumor cells. We further demonstrated that GAT3 interacted with calmodulin, a pivotal regulator of PMCA4, and this interaction was decreased following 24 h GABA treatment. Long-term GABA stimulation also disrupted PMCA4/GAT3 complex, overloaded lipid rafts with Ca²⁺ and decreased glioma invasiveness in the presence of PMCA4. In these conditions, we observed GAT3- and Ca²⁺/calmodulin-dependent protein kinase II-dependent CREB phosphorylation at Ser133, which was controlled by Ca²⁺ events in lipid rafts and required to maintain glioma invasiveness. Our study uncovers a previously unrecognized GAT3-dependent mechanism of Ca²⁺compartmentalization in membrane microdomains, shedding new light on its potential role in tumor behavior. Understanding these local Ca²⁺ signaling partnerships will offer valuable insights into gliomagenesis and could lead to the development of novel therapeutic strategies for glioma treatment.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"130 ","pages":"Article 103050"},"PeriodicalIF":4.3,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144490793","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 at the crossroads: TPC2’s role in LRRK2-linked Parkinson’s disease","authors":"Federica De Lazzari ,&nbsp;Simone Wanderoy ,&nbsp;Alexander J Whitworth","doi":"10.1016/j.ceca.2025.103049","DOIUrl":"10.1016/j.ceca.2025.103049","url":null,"abstract":"<div><div>The pathogenic mechanisms of LRRK2 are hotly debated but regulation of lysosomal homeostasis has emerged as a leading focus area. In recent work, Gregori et al. show that Ca²⁺ release through the lysosomal Two-Pore Channel 2 (TPC2) could be a significant contributor to dopaminergic neuron vulnerability.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"130 ","pages":"Article 103049"},"PeriodicalIF":4.3,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144481519","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":"Paclitaxel activates SOCE/ICRAC in dorsal root ganglion neurons: implications for paclitaxel-induced peripheral neuropathy","authors":"Marta Delconti ,&nbsp;Tiziana Ravasenga ,&nbsp;Marianna Dionisi ,&nbsp;Tiziana Romanazzi ,&nbsp;Fausto Chiazza ,&nbsp;Silvia Giatti ,&nbsp;Dmitry Lim ,&nbsp;Armando A. Genazzani ,&nbsp;Beatrice Riva ,&nbsp;Cristina Meregalli ,&nbsp;Guido Cavaletti ,&nbsp;Carla Distasi","doi":"10.1016/j.ceca.2025.103040","DOIUrl":"10.1016/j.ceca.2025.103040","url":null,"abstract":"<div><div>Paclitaxel (PTX) is one of the most widely used antineoplastic drugs for the treatment of solid cancers. Its mechanism of action involves binding to β-tubulin subunits, leading to the stabilization of microtubule polymers and subsequent cell cycle arrest. Despite its efficacy, PTX is associated with significant adverse effects, most notably peripheral neurotoxicity and neuropathic pain, which represent the primary dose-limiting side effects. In sensory neurons, PTX affects multiple molecular pathways, with early alterations in excitability and calcium signaling following acute drug exposure. To investigate these mechanisms, we employed a combination of calcium imaging, electrophysiological techniques, and pharmacological approaches to explore the role of ORAI channels in the excitability and calcium dynamics of mouse dorsal root ganglion neurons. Our findings reveal that acute exposure to low doses of PTX triggers IP₃-dependent calcium release and activates a store-operated calcium entry through STIM-ORAI dependent I_CRAC. Moreover, acute PTX application induced the activation of a sustained calcium inward current, V_m depolarization and triggered action potential firing that was strongly attenuated by I_CRAC inhibition. Molecular analyses further revealed a significant upregulation of <em>Orai1, Orai2</em>, and <em>Stim2</em> mRNA levels, accompanied by elevated ORAI1 protein expression, in a rat model of paclitaxel-induced peripheral neuropathy. These results suggest that ORAI and STIM proteins represent promising molecular targets for developing therapies aimed at mitigating the side effects of PTX.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"130 ","pages":"Article 103040"},"PeriodicalIF":4.3,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144190172","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":"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}