Cell calcium最新文献

{"title":"STIM2 variants regulate Orai1/TRPC1/TRPC4-mediated store-operated Ca2+ entry and mitochondrial Ca2+ homeostasis in cardiomyocytes","authors":"Rui Luo ,&nbsp;Pauline Le Gourriérec ,&nbsp;Fabrice Antigny ,&nbsp;Kaveen Bedouet ,&nbsp;Séverine Domenichini ,&nbsp;Ana-Maria Gomez ,&nbsp;Jean-Pierre Benitah ,&nbsp;Jessica Sabourin","doi":"10.1016/j.ceca.2024.102871","DOIUrl":"10.1016/j.ceca.2024.102871","url":null,"abstract":"<div><p>The stromal interaction molecules (STIMs) are the sarcoplasmic reticulum (SR) Ca²⁺ sensors that trigger store-operated Ca²⁺ entry (SOCE) in a variety of cell types. While STIM1 isoform has been the focus of the research in cardiac pathophysiology, the function of the homolog STIM2 remains unknown. Using Ca²⁺ imaging and patch-clamp techniques, we showed that knockdown (KD) of STIM2 by siRNAs increased SOCE and the <em>I</em>_SOC current in neonatal rat ventricular cardiomyocytes (NRVMs). Within this cardiomyocyte model, we identified the transcript expression of <em>Stim2.1</em> and <em>Stim2.2</em> splice variants, with predominance for <em>Stim2.2</em>. Using conventional and super-resolution confocal microscopy (STED), we found that exogenous STIM2.1 and STIM2.2 formed pre-clusters with a reticular organization at rest. Following SR Ca²⁺ store depletion, some STIM2.1 and STIM2.2 clusters were translocated to SR-plasma membrane (PM) junctions and co-localized with Orai1. The overexpression strategy revealed that STIM2.1 suppressed Orai1-mediated SOCE and the <em>I</em>_SOC current while STIM2.2 enhanced SOCE. STIM2.2-enhanced SOCE was also dependent on TRPC1 and TRPC4. Even if STIM2 KD or splice variants overexpression did not affect cytosolic Ca²⁺ cycling, we observed, using Rhod-2/AM Ca²⁺ imaging, that Orai1 inhibition or STIM2.1 overexpression abolished the mitochondrial Ca²⁺ (mCa²⁺) uptake, as opposed to STIM2 KD. We also found that STIM2 was present in the mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) by interacting with the inositol trisphosphate receptors (IP₃Rs), voltage-dependent anion channel (VDAC), mitochondrial Ca²⁺ uniporter (MCU), and mitofusin-2 (MNF2). Our results suggested that, in NRVMs, STIM2.1 constitutes the predominant functional variant that negatively regulates Orai1-generated SOCE. It participates in the control of mCa²⁺ uptake capacity possibly via the STIM2-IP₃Rs-VDAC-MCU and MNF2 complex.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"119 ","pages":"Article 102871"},"PeriodicalIF":4.0,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0143416024000290/pdfft?md5=11d1caa8cf0ca123f3dc1df14867cc62&pid=1-s2.0-S0143416024000290-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140169337","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":"Ruthenium red: Blocker or antagonist of TRPV channels?","authors":"Andrés Jara-Oseguera","doi":"10.1016/j.ceca.2024.102874","DOIUrl":"10.1016/j.ceca.2024.102874","url":null,"abstract":"<div><p>Ruthenium red (RR) is a widely used inhibitor of Transient Receptor Potential (TRP) cation channels and other types of ion channels. Although RR has been generally accepted to inhibit TRP channels by physically blocking the ion permeation pathway, recent structural evidence suggests that it might also function as an antagonist, inducing conformational changes in the channel upon binding that result in closure of the pore. In a recent manuscript published in EMBO Reports, Ruth A. Pumroy and collaborators solve structures of TRPV2 and TRPV5 channels in the presence and absence of activators and RR. The data sheds light on the mechanism of inhibition by RR, while also opening new questions for further investigation.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"119 ","pages":"Article 102874"},"PeriodicalIF":4.0,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140154348","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":"Sleep, calcium and microglia – an (un)expected liaison","authors":"Olga Garaschuk ,&nbsp;Alexei Verkhratsky","doi":"10.1016/j.ceca.2024.102872","DOIUrl":"10.1016/j.ceca.2024.102872","url":null,"abstract":"","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"119 ","pages":"Article 102872"},"PeriodicalIF":4.0,"publicationDate":"2024-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140105219","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: Receptor structure, activation, modulation and role in neuro-immune interactions and pain","authors":"Thaila Kawane Euflazio Maximiano ,&nbsp;Jessica Aparecida Carneiro ,&nbsp;Victor Fattori ,&nbsp;Waldiceu A. Verri","doi":"10.1016/j.ceca.2024.102870","DOIUrl":"10.1016/j.ceca.2024.102870","url":null,"abstract":"<div><p>In the 1990s, the identification of a non-selective ion channel, especially responsive to capsaicin, revolutionized the studies of somatosensation and pain that were to follow. The TRPV1 channel is expressed mainly in neuronal cells, more specifically, in sensory neurons responsible for the perception of noxious stimuli. However, its presence has also been detected in other non-neuronal cells, such as immune cells, β- pancreatic cells, muscle cells and adipocytes. Activation of the channel occurs in response to a wide range of stimuli, such as noxious heat, low pH, gasses, toxins, endocannabinoids, lipid-derived endovanilloid, and chemical agents, such as capsaicin and resiniferatoxin. This activation results in an influx of cations through the channel pore, especially calcium. Intracellular calcium triggers different responses in sensory neurons. Dephosphorylation of the TRPV1 channel leads to its desensitization, which disrupts its function, while its phosphorylation increases the channel's sensitization and contributes to the channel's rehabilitation after desensitization. Kinases, phosphoinositides, and calmodulin are the main signaling pathways responsible for the channel's regulation. Thus, in this review we provide an overview of TRPV1 discovery, its tissue expression as well as on the mechanisms by which TRPV1 activation (directly or indirectly) induces pain in different disease models.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"119 ","pages":"Article 102870"},"PeriodicalIF":4.0,"publicationDate":"2024-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140076075","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":"Neighbourhood Watch: Two-pore-2 channels talking to IP3 receptors","authors":"David N Criddle,&nbsp;Alexei V Tepikin","doi":"10.1016/j.ceca.2024.102868","DOIUrl":"https://doi.org/10.1016/j.ceca.2024.102868","url":null,"abstract":"<div><p>The recent elegant study by Y. Yuan and colleagues examined functional relationships between the lysosomal two-pore channels 2 (TPC2) and IP3 receptors (IP3Rs) located in the endoplasmic reticulum <span>[1]</span>. The findings of this study suggest functional coupling of these channels and receptors. The study also describes interesting novel phenomena, which may indicate an additional coupling mechanism.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"119 ","pages":"Article 102868"},"PeriodicalIF":4.0,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140062862","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":"Recognition of granulocyte-macrophage colony-stimulating factor by specific S100 proteins","authors":"Alexey S. Kazakov ,&nbsp;Victoria A. Rastrygina ,&nbsp;Alisa A. Vologzhannikova ,&nbsp;Marina Y. Zemskova ,&nbsp;Lolita A. Bobrova ,&nbsp;Evgenia I. Deryusheva ,&nbsp;Maria E. Permyakova ,&nbsp;Andrey S. Sokolov ,&nbsp;Ekaterina A. Litus ,&nbsp;Marina P. Shevelyova ,&nbsp;Vladimir N. Uversky ,&nbsp;Eugene A. Permyakov ,&nbsp;Sergei E. Permyakov","doi":"10.1016/j.ceca.2024.102869","DOIUrl":"10.1016/j.ceca.2024.102869","url":null,"abstract":"<div><p>Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic myelopoietic growth factor and proinflammatory cytokine, clinically used for multiple indications and serving as a promising target for treatment of many disorders, including cancer, multiple sclerosis, rheumatoid arthritis, psoriasis, asthma, COVID-19. We have previously shown that dimeric Ca²⁺-bound forms of S100A6 and S100P proteins, members of the multifunctional S100 protein family, are specific to GM-CSF. To probe selectivity of these interactions, the affinity of recombinant human GM-CSF to dimeric Ca²⁺-loaded forms of 18 recombinant human S100 proteins was studied by surface plasmon resonance spectroscopy. Of them, only S100A4 protein specifically binds to GM-CSF with equilibrium dissociation constant, <em>K</em>_d, values of 0.3–2 μM, as confirmed by intrinsic fluorescence and chemical crosslinking data. Calcium removal prevents S100A4 binding to GM-CSF, whereas monomerization of S100A4/A6/P proteins disrupts S100A4/A6 interaction with GM-CSF and induces a slight decrease in S100P affinity for GM-CSF. Structural modelling indicates the presence in the GM-CSF molecule of a conserved S100A4/A6/P-binding site, consisting of the residues from its termini, helices I and III, some of which are involved in the interaction with GM-CSF receptors. The predicted involvement of the ‘hinge’ region and F89 residue of S100P in GM-CSF recognition was confirmed by mutagenesis. Examination of S100A4/A6/P ability to affect GM-CSF signaling showed that S100A4/A6 inhibit GM-CSF-induced suppression of viability of monocytic THP-1 cells. The ability of the S100 proteins to modulate GM-CSF activity is relevant to progression of various neoplasms and other diseases, according to bioinformatics analysis. The direct regulation of GM-CSF signaling by extracellular forms of the S100 proteins should be taken into account in the clinical use of GM-CSF and development of the therapeutic interventions targeting GM-CSF or its receptors.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"119 ","pages":"Article 102869"},"PeriodicalIF":4.0,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140076039","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":"Corrigendum to “Mutations and clinical significance of calcium voltage-gated channel subunit alpha 1E (CACNA1E) in non-small cell lung cancer” [Cell Calcium 102 (2022) 102527]","authors":"SH Gao ,&nbsp;GZ Wang ,&nbsp;LP Wang ,&nbsp;L Feng ,&nbsp;YC Zhou ,&nbsp;XJ Yu ,&nbsp;F Liang ,&nbsp;FY Yang ,&nbsp;Z Wang ,&nbsp;BB Sun ,&nbsp;D Wang ,&nbsp;LJ Liang ,&nbsp;DW Xie ,&nbsp;S Zhao ,&nbsp;HP Feng ,&nbsp;X Li ,&nbsp;KK Li ,&nbsp;TS Tang ,&nbsp;YC Huang ,&nbsp;SQ Wang ,&nbsp;GB Zhou","doi":"10.1016/j.ceca.2024.102866","DOIUrl":"https://doi.org/10.1016/j.ceca.2024.102866","url":null,"abstract":"","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"119 ","pages":"Article 102866"},"PeriodicalIF":4.0,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0143416024000241/pdfft?md5=c47ac62f359793f132f1fff0b81a0ea3&pid=1-s2.0-S0143416024000241-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139999790","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":"Newly uncovered Cryo-EM structures of mammalian NCXs set a new stage for resolving the underlying molecular mechanisms and drug discovery","authors":"Daniel Khananshvili","doi":"10.1016/j.ceca.2024.102867","DOIUrl":"https://doi.org/10.1016/j.ceca.2024.102867","url":null,"abstract":"<div><p>The membrane-abundant NCX proteins mediate an electrogenic ion exchange (3Na⁺:1Ca²⁺) in the Ca²⁺-exit or Ca²⁺-entry mode. The structurally related isoform/splice variants of NCX are expressed in a tissue-specific manner to shape Ca²⁺ signalling/homeostasis in diverse cell types. The lack of mammalian NCX structure hampered the functional and regulatory resolution of tissue-specific NCX variants and their pharmacological targeting. Recently unveiled Cryo-EM structures of human cardiac NCX1.1[1] and kidney NCX1.3[2] provide new opportunities for resolving structure/functional divergences among NCX variants and their pharmacological targeting.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"119 ","pages":"Article 102867"},"PeriodicalIF":4.0,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139993160","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":"NMDA receptor-mediated Ca2+ signaling: Impact on cell cycle regulation and the development of neurodegenerative diseases and cancer","authors":"Ana L. González-Cota ,&nbsp;Daniel Martínez-Flores ,&nbsp;Margarita Jacaranda Rosendo-Pineda ,&nbsp;Luis Vaca","doi":"10.1016/j.ceca.2024.102856","DOIUrl":"10.1016/j.ceca.2024.102856","url":null,"abstract":"<div><p>NMDA receptors are Ca²⁺-permeable ligand-gated ion channels that mediate fast excitatory transmission in the central nervous system. NMDA receptors regulate the proliferation and differentiation of neural progenitor cells and also play critical roles in neural plasticity, memory, and learning. In addition to their physiological role, NMDA receptors are also involved in glutamate-mediated excitotoxicity, which results from excessive glutamate stimulation, leading to Ca²⁺ overload, and ultimately to neuronal death. Thus, NMDA receptor-mediated excitotoxicity has been linked to several neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, dementia, and stroke. Interestingly, in addition to its effects on cell death, aberrant expression or activation of NMDA receptors is also involved in pathological cellular proliferation, and is implicated in the invasion and proliferation of various types of cancer. These disorders are thought to be related to the contribution of NMDA receptors to cell proliferation and cell death through cell cycle modulation. This review aims to discuss the evidence implicating NMDA receptor activity in cell cycle regulation and the link between aberrant NMDA receptor activity and the development of neurodegenerative diseases and cancer due to cell cycle dysregulation. The information presented here will provide insights into the signaling pathways and the contribution of NMDA receptors to these diseases, and suggests that NMDA receptors are promising targets for the prevention and treatment of these diseases, which are leading causes of death and disability worldwide.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"119 ","pages":"Article 102856"},"PeriodicalIF":4.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139874260","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":"SERCA-1 conformational change exerted by the Ca2+-channel blocker diltiazem affects mammalian skeletal muscle function","authors":"Aura Jiménez-Garduño ,&nbsp;Ibrahim Ramirez-Soto ,&nbsp;Ileana Miranda-Rodríguez ,&nbsp;Sofía Gitler ,&nbsp;Alicia Ortega","doi":"10.1016/j.ceca.2024.102852","DOIUrl":"10.1016/j.ceca.2024.102852","url":null,"abstract":"<div><p>In skeletal muscle (SM), inward Ca²⁺-currents have no apparent role in excitation-contraction coupling (e-c coupling), however the Ca²⁺-channel blocker can affect twitch and tetanic muscle in mammalian SM. Experiments were conducted to study how diltiazem (DLZ) facilitates e-c coupling and inhibits contraction. 1) In complete <em>Extensor Digitorum Longus</em> (EDL) muscle and single intact fibres, 0.03 mM DLZ causes twitch potentiation and decreases force during tetanic activity, with increased fatigue. 2) In split open fibres isolated from EDL fibres, DLZ inhibits sarcoplasmic reticulum (SR) Ca²⁺-loading in a dose-dependent manner and has a potentiating effect on caffeine-induced SR Ca²⁺-release. 3) In isolated light SR (LSR) vesicles, SERCA1 hydrolytic activity is not affected by DLZ up to 0.2 mM. However, ATP-dependent Ca²⁺-uptake was inhibited in a dose-dependent manner at a concentration where e-c coupling is changed. 4) The passive Ca²⁺-efflux from LSR was reduced by half with 0.03 mM diltiazem, indicating that SR leaking does not account for the decreased Ca²⁺-uptake. 5) The denaturation profile of the SERCA Ca²⁺-binding domain has lower thermal stability in the presence of DLZ in a concentration-dependent manner, having no effect on the nucleotide-binding domain. We conclude that the effect of DLZ on SM is exerted by crossing the sarcolemma and interacting directly with the SERCA Ca²⁺-binding domain, affecting SR Ca²⁺-loading during relaxation, which has a consequence on SM contractility. Diltiazem effect on SM could be utilized as a tool to understand SM e-c coupling and muscle fatigue.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"119 ","pages":"Article 102852"},"PeriodicalIF":4.0,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139823544","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}