Cell calcium最新文献

{"title":"Protein diversity in store-operated calcium entry components and their related variants.","authors":"Mélanie Robitaille","doi":"10.1016/j.ceca.2025.103066","DOIUrl":"10.1016/j.ceca.2025.103066","url":null,"abstract":"<p><p>Protein diversity is a fundamental biological process that enhances the functional complexity of cellular signaling pathways. This diversity arises through multiple molecular mechanisms such as gene duplication, alternative splicing, and alternative translation initiation, which together expand the proteome landscape. Calcium signaling showcases this diversity, with several channels, pumps, and regulatory proteins expressed as multiple isoforms and variants. Within the store-operated calcium entry pathway, protein diversity is evident in the existence of distinct paralogs of ORAI channels and STIM proteins. The additional presence of numerous isoforms and variants of ORAI and STIM shapes the store-operated calcium entry pathway, providing flexibility to cellular calcium regulation in various contexts. Deciphering how protein diversity modulates store-operated calcium entry function is essential for advancing our understanding of calcium signaling in both health and disease.</p>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"131 ","pages":"103066"},"PeriodicalIF":4.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811841","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":"Histamine 1 receptors and reverse-mode Na+/Ca2+ exchanger drive extracellular Na+-dependent intracellular Ca2+ oscillations in human cerebrovascular endothelial cells","authors":"Valentina Brunetti ,&nbsp;Roberto Berra-Romani ,&nbsp;Nayeli Coyotl-Santiago ,&nbsp;Yair Esquitin-Gonzalez ,&nbsp;Giorgia Chinigò ,&nbsp;Gerardo Rosario Biella ,&nbsp;Francesco Moccia ,&nbsp;Giorgia Scarpellino","doi":"10.1016/j.ceca.2025.103067","DOIUrl":"10.1016/j.ceca.2025.103067","url":null,"abstract":"<div><div>Cerebrovascular endothelial cells represent the core component of the blood-brain barrier, (BBB) which plays a critical role in regulating the local ionic microenvironment around the synapses. Therefore, cerebrovascular endothelial cells experience dramatic changes in the extracellular concentrations of potassium and sodium ions during intense neuronal firing or pathological conditions, such as spreading depression.</div><div>Herein, we assessed the mechanisms by which a reduction in extracellular sodium concentration ([Na⁺]_o) triggers complex Ca²⁺ signals in the hCMEC/D3 cell line, which is the most widespread model of human BBB.</div><div>We demonstrate that lowering the [Na⁺]_o elicits a variety of Ca²⁺ signals, including monotonic increases in intracellular Ca²⁺ concentration ([Ca²⁺]_i) and repetitive oscillations in [Ca²⁺]_i, which are triggered by the reverse-mode Na⁺/Ca²⁺ exchanger and histamine 1 receptor (H1R). Furthermore, we provide the first evidence that H1R may play a critical role in translating a reduction in [Na⁺]_o into the activation of phospholipase C and following production of inositol triphosphate (InsP₃), thereby inducing the rhythmic activation of InsP₃ receptors on the endoplasmic reticulum (ER) and progressive depletion of the ER Ca²⁺ pool. The fall in the ER Ca²⁺ concentration leads to quick Store-Operated Ca²⁺ Entry activation, which maintains the intracellular Ca²⁺ oscillations by rapidly refilling the ER Ca²⁺ store. The endothelial Ca²⁺ oscillations induced by the reduction in [Na⁺]_o may then lead to nitric oxide release.</div><div>These findings, therefore, shed novel light on the mechanisms whereby G_q protein coupled receptors (G_qPCRs) can shape endothelial Ca²⁺ signaling and Ca²⁺-dependent events at the human neurovascular unit.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"131 ","pages":"Article 103067"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144886537","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":"NAADP-mediated calcium release promotes angiopoietin 2 secretion by regulating Rab46-dependent Weibel-Palade body trafficking","authors":"Ryan D. Murray ,&nbsp;Melissa Rose ,&nbsp;Katarina T. Miteva ,&nbsp;David J. Beech ,&nbsp;Lynn McKeown","doi":"10.1016/j.ceca.2025.103068","DOIUrl":"10.1016/j.ceca.2025.103068","url":null,"abstract":"<div><div>Angiopoietin2 (Ang2), a regulator of angiogenesis, is stored with other pro-inflammatory and pro-thrombotic mediators, in endothelial-specific vesicles called Weibel-Palade bodies (WPBs). Acute stimulation of endothelial cells with histamine, delays Ang2 secretion by activating Rab46-specific trafficking of Ang2-containing WPBs to the microtubule organising centre (MTOC), where they persist until Ca²⁺ binds to the EF-hand of Rab46, enabling detachment. Here, using Ca²⁺ imaging and high-resolution light microscopy, we pharmacologically investigated the contribution of endolysosomal two-pore channel proteins (TPC) to the Ca²⁺ signal necessary for WPB detachment and Ang2 secretion. We show an increase in the histamine-evoked clustering of Rab46 (and thus WPBs) at the MTOC in the presence of TPC inhibitors Ned-19 and tetrandrine, and a decrease in the presence of a TPC2 agonist, TPC2-A1-N. Histamine-evoked secretion of Ang2 was decreased by pharmacological inhibition of TPC channels but potentiated in the presence of TPC2-A1-N. These data suggest that histamine-mediated Ca²⁺ release via TPC2 channels is necessary for the Rab46-dependent detachment of Ang2-positive WPBs from the MTOC and thus Ang2 secretion.</div></div><div><h3>Summary</h3><div>Ca²⁺ binding to the EF-hand of Rab46 in endothelial cells has previously been reported but the molecular mechanisms and functional relevance are unclear. Here, the authors show that Ca²⁺ released from TPC channels regulates the detachment of Rab46-positive WPBs from the MTOC, which thereby promotes secretion of Ang2.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"131 ","pages":"Article 103068"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144892187","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":"TRPV1 signaling in skeletal muscle: A mini review of physiological and pathological roles.","authors":"Xiaoqing Ding, Chenyu Zhu, Qi Lu, Yuhao Zhang, Binghong Gao","doi":"10.1016/j.ceca.2025.103057","DOIUrl":"10.1016/j.ceca.2025.103057","url":null,"abstract":"<p><p>Transient receptor potential vanilloid subtype 1 (TRPV1) is a non-selective cation channel that is mainly sensitive to stimuli such as high temperature, acidic environment, and capsaicin. Studies have reported that TRPV1 is expressed in skeletal muscle tissues and is involved in the regulation of a variety of physiological and pathological processes in skeletal muscle, but its regulatory mechanisms have not been analyzed and discussed. For this reason, we summarized the role of TRPV1 in skeletal muscle function and the mechanism of its influence on skeletal muscle-related physiopathological changes, such as myotube formation, inflammation, autophagy, mitochondrial biogenesis, and energy metabolism, which provides a theoretical basis and therapeutic target for understanding TRPV1 regulation of skeletal muscle-related diseases.</p>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"131 ","pages":"103057"},"PeriodicalIF":4.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811842","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":"2025-09-01","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":"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":"2025-09-01","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":"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":"2025-09-01","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":"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":"2025-09-01","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":"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":"2025-09-01","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":"Copine A is essential for calcium homeostasis in Dictyostelium","authors":"Amber D. Ide ,&nbsp;Cody T. Morrison ,&nbsp;Christer A. Carne ,&nbsp;Cynthia K. Damer","doi":"10.1016/j.ceca.2025.103055","DOIUrl":"10.1016/j.ceca.2025.103055","url":null,"abstract":"<div><div>Copines are a family of calcium-dependent phospholipid-binding proteins found in most eukaryotic organisms. The expression of multiple copine genes is dysregulated in various types of human cancers. Yet, a common mechanistic function for copines remains enigmatic. We are studying copines in <em>Dictyostelium</em>, which has six copine genes (<em>cpnA-cpnF</em>). Cells lacking <em>cpnA</em> (<em>cpnA-</em>) exhibit many phenotypes including defects in development, chemotaxis, adhesion, and contractile vacuole (CV) function. In this study, we identified a novel link between CpnA and calcium homeostasis. We found that <em>cpnA-</em> cells have more phosphatidylserine (PS) exposed in the outer leaflet of the plasma membrane due to having an increased intracellular calcium concentration. The PS exposure defect and the enlarged CV defect in <em>cpnA-</em> cells were rescued by chelating calcium. We further investigated the role of PatA, a CV-localized Ca²⁺-ATPase responsible for pumping calcium into the CV. Although <em>cpnA-</em> cells expressed normal levels of <em>patA</em>, immunofluorescence revealed reduced PatA localization to the CV membrane. Notably, <em>patA</em> knockdown (<em>patA^KD</em>) cells phenocopied <em>cpnA-</em> cells, displaying enlarged CVs, elevated intracellular calcium, and increased PS exposure. Taken together, our findings suggest that CpnA promotes calcium sequestration into the CV, likely by regulating PatA localization or activity. This role in calcium homeostasis provides a mechanistic framework for understanding copine function and offers insight into how calcium dysregulation associated with copines may contribute to cancer progression.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"130 ","pages":"Article 103055"},"PeriodicalIF":4.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144687286","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}