Cell calcium最新文献

{"title":"Targeting calciumopathy for neuroprotection: focus on calcium channels Cav1, Orai1 and P2X7","authors":"Myriam Torres-Rico ,&nbsp;Virginia García-Calvo ,&nbsp;Adrián Gironda-Martínez ,&nbsp;Jorge Pascual-Guerra ,&nbsp;Antonio G. García ,&nbsp;Victoria Maneu","doi":"10.1016/j.ceca.2024.102928","DOIUrl":"https://doi.org/10.1016/j.ceca.2024.102928","url":null,"abstract":"<div><p>As the uncontrolled entry of calcium ions (Ca²⁺) through plasmalemmal calcium channels is a cell death trigger, the conjecture is here raised that mitigating such an excess of Ca²⁺ entry should rescue from death the vulnerable neurons in neurodegenerative diseases (NDDs). However, this supposition has failed in some clinical trials (CTs). Thus, a recent CT tested whether isradipine, a blocker of the Cav1 subtype of voltage-operated calcium channels (VOCCs), exerted a benefit in patients with Parkinson's disease (PD); however, outcomes were negative. This is one more of the hundreds of CTs done under the principle of one-drug-one-target, that have failed in Alzheimer's disease (AD) and other NDDs during the last three decades. As there are myriad calcium channels to let Ca²⁺ ions gain the cell cytosol, it seems reasonable to predict that blockade of Ca²⁺ entry through a single channel may not be capable of preventing the Ca²⁺ flood of cells by the uncontrolled Ca²⁺ entry. Furthermore, as Ca²⁺ signaling is involved in the regulation of myriad functions in different cell types, it seems also reasonable to guess that a therapy should be more efficient by targeting different cells with various drugs. Here, we propose to mitigate Ca²⁺ entry by the simultaneous partial blockade of three quite different subtypes of plasmalemmal calcium channels that is, the Cav1 subtype of VOCCs, the Orai1 store-operated calcium channel (SOCC), and the purinergic P2X7 calcium channel. All three channels are expressed in both microglia and neurons. Thus, by targeting the three channels with a combination of three drug blockers we expect favorable changes in some of the pathogenic features of NDDs, namely (i) to mitigate Ca²⁺ entry into microglia; (ii) to decrease the Ca²⁺-dependent microglia activation; (iii) to decrease the sustained neuroinflammation; (iv) to decrease the uncontrolled Ca²⁺ entry into neurons; (v) to rescue vulnerable neurons from death; and (vi) to delay disease progression. In this review we discuss the arguments underlying our triad hypothesis in the sense that the combination of three repositioned medicines targeting Cav1, Orai1, and P2X7 calcium channels could boost neuroprotection and delay the progression of AD and other NDDs.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"123 ","pages":"Article 102928"},"PeriodicalIF":4.3,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0143416024000861/pdfft?md5=11c1d21faaeacd324f82d6a1903836b4&pid=1-s2.0-S0143416024000861-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141607645","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 frozen portrait of a warm channel","authors":"Brett Boonen,&nbsp;Thomas Voets","doi":"10.1016/j.ceca.2024.102927","DOIUrl":"10.1016/j.ceca.2024.102927","url":null,"abstract":"<div><p>In order to understand protein function, the field of structural biology makes extensive use of cryogenic electron microscopy (cryo-EM), a technique that enables structure determination at atomic resolution following embedding of protein particles in vitreous ice. Considering the profound effects of temperature on macromolecule function, an important—but often neglected-question is how the frozen particles relate to the actual protein conformations at physiological temperatures. In a recent study, Hu et al. compare structures of the cation channel TRPM4 “frozen” at 4 °C versus 37 °C, revealing how temperature critically affects the binding of activating Ca²⁺ ions and other channel modulators.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"123 ","pages":"Article 102927"},"PeriodicalIF":4.3,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141497161","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":"STIM1: A new player in nuclear dynamics? Lessons learnt from tubular aggregate myopathy","authors":"Emanuela Pessolano ,&nbsp;Zlata A. Sosic ,&nbsp;Armando A. Genazzani","doi":"10.1016/j.ceca.2024.102926","DOIUrl":"10.1016/j.ceca.2024.102926","url":null,"abstract":"<div><p>Two recent papers have highlighted that STIM1, a key component of Store-operated Ca2+-entry, is able to translocate to the nucleus and participate in nuclear Ca²⁺-handling and in DNA repair. These finding opens new avenues on the role that this Ca²⁺-sensing protein may have in health and disease.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"123 ","pages":"Article 102926"},"PeriodicalIF":4.3,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141497162","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":"Anoctamin 1, a multi-modal player in pain and itch","authors":"Hyungsup Kim ,&nbsp;Won-Sik Shim ,&nbsp;Uhtaek Oh","doi":"10.1016/j.ceca.2024.102924","DOIUrl":"10.1016/j.ceca.2024.102924","url":null,"abstract":"<div><p>Anoctamin 1 (ANO1/TMEM16A) encodes a Ca²⁺-activated Cl^- channel. Among ANO1′s many physiological functions, it plays a significant role in mediating nociception and itch. ANO1 is activated by intracellular Ca²⁺ and depolarization. Additionally, ANO1 is activated by heat above 44 °C, suggesting heat as another activation stimulus. ANO1 is highly expressed in nociceptors, indicating a role in nociception. Conditional Ano1 ablation in dorsal root ganglion (DRG) neurons results in a reduction in acute thermal pain, as well as thermal and mechanical allodynia or hyperalgesia evoked by inflammation or nerve injury. Pharmacological interventions also lead to a reduction in nocifensive behaviors. ANO1 is functionally linked to the bradykinin receptor and TRPV1. Bradykinin stimulates ANO1 via IP3-mediated Ca²⁺ release from intracellular stores, whereas TRPV1 stimulates ANO1 via a combination of Ca²⁺ influx and release. Nerve injury causes upregulation of ANO1 expression in DRG neurons, which is blocked by ANO1 antagonists. Due to its role in nociception, strong and specific ANO1 antagonists have been developed. ANO1 is also expressed in pruritoceptors, mediating Mas-related G protein-coupled receptors (Mrgprs)-dependent itch. The activation of ANO1 leads to chloride efflux and depolarization due to high intracellular chloride concentrations, causing pain and itch. Thus, ANO1 could be a potential target for the development of new drugs treating pain and itch.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"123 ","pages":"Article 102924"},"PeriodicalIF":4.3,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0143416024000824/pdfft?md5=423b075f13875d438ee3a3b93e33c9dc&pid=1-s2.0-S0143416024000824-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141514353","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":"Loss-of-function W4645R mutation in the RyR2-caffeine binding site: implications for synchrony and arrhythmogenesis","authors":"José-Carlos Fernández-Morales ,&nbsp;Noemi Toth ,&nbsp;Pinar Bayram ,&nbsp;Taylor Rienzo ,&nbsp;Martin Morad","doi":"10.1016/j.ceca.2024.102925","DOIUrl":"https://doi.org/10.1016/j.ceca.2024.102925","url":null,"abstract":"<div><h3>Aims</h3><p>Previous studies have identified RyR2 W4645R mutation, located in the caffeine-binding site, to associate with CPVT1 pathology. Caffeine binding to its site is thought to displace the carboxyl-terminal domain to Ca²⁺-binding, allowing the tryptophan residue (W4645) to regulate Ca²⁺ sensitivity of RyR2. To gain insights into regulation of RyR2 Ca²⁺-binding and its interaction with caffeine-binding site, we introduced W4645R-RyR2 point mutation via CRISPR/Cas9 gene-editing in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC<img>CMs) and characterized their Ca²⁺-signaling phenotype compared to WT hiPSC<img>CMs.</p></div><div><h3>Methods and Results</h3><p>W4645R-RyR2 cardiomyocytes had: <strong>(1)</strong> no significant change in I_Ca magnitude or voltage-dependence; <strong>(2)</strong> slightly reduced CICR; <strong>(3)</strong> altered relaxation kinetics of Ca²⁺-transients with no change in isoproterenol sensitivity; <strong>(4)</strong> complete loss of caffeine-triggered Ca²⁺ release; (<strong>5</strong>) larger SR Ca²⁺ leak resulting in 40 % lower SR Ca²⁺ content, as determined by myocytes’ response to 4-CmC; <strong>(6)</strong> lower incidence of calcium sparks and asynchronous spontaneous SR Ca²⁺ releases.</p></div><div><h3>Conclusions</h3><p>W4645R-RyR2 mutation induces loss of caffeine-triggered SR Ca²⁺ release and enhances SR Ca²⁺ leak that underlie asynchronous spontaneous Ca²⁺ releases, triggering arrhythmia and impairing cardiac function.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"123 ","pages":"Article 102925"},"PeriodicalIF":4.3,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141438113","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":"ER and SOCE Ca2+ signals are not required for directed cell migration in human iPSC-derived microglia","authors":"Alberto Granzotto ,&nbsp;Amanda McQuade ,&nbsp;Jean Paul Chadarevian ,&nbsp;Hayk Davtyan ,&nbsp;Stefano L. Sensi ,&nbsp;Ian Parker ,&nbsp;Mathew Blurton-Jones ,&nbsp;Ian F. Smith","doi":"10.1016/j.ceca.2024.102923","DOIUrl":"10.1016/j.ceca.2024.102923","url":null,"abstract":"<div><p>The central nervous system (CNS) is constantly surveilled by microglia, highly motile and dynamic cells deputed to act as the first line of immune defense in the brain and spinal cord. Alterations in the homeostasis of the CNS are detected by microglia that respond by extending their processes or – following major injuries – by migrating toward the affected area. Understanding the mechanisms controlling directed cell migration of microglia is crucial to dissect their responses to neuroinflammation and injury. We used a combination of pharmacological and genetic approaches to explore the involvement of calcium (Ca²⁺) signaling in the directed migration of human induced pluripotent stem cell (iPSC)-derived microglia challenged with a purinergic stimulus. This approach mimics cues originating from injury of the CNS. Unexpectedly, simultaneous imaging of microglia migration and intracellular Ca²⁺ changes revealed that this phenomenon does not require Ca²⁺ signals generated from the endoplasmic reticulum (ER) and store-operated Ca²⁺ entry (SOCE) pathways. Instead, we find evidence that human microglial chemotaxis to purinergic signals is mediated by cyclic AMP in a Ca²⁺-independent manner. These results challenge prevailing notions, with important implications in neurological conditions characterized by perturbation in Ca²⁺ homeostasis.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"123 ","pages":"Article 102923"},"PeriodicalIF":4.3,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0143416024000812/pdfft?md5=9ff12728479ef08c1f3bfb7244bdd1f8&pid=1-s2.0-S0143416024000812-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141405364","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":"GPR30 is a potential player between islet cells and ductal HCO3− secretion","authors":"Viktória Venglovecz ,&nbsp;Péter Hegyi","doi":"10.1016/j.ceca.2024.102922","DOIUrl":"10.1016/j.ceca.2024.102922","url":null,"abstract":"<div><p>The primary role of pancreatic ductal HCO₃⁻ secretion is to prevent premature activation of digestive enzymes and to provide a vehicle for the delivery of enzymes to the duodenum. In addition, HCO₃⁻is responsible for the neutralization of gastric juice and protect against the formation of protein plugs and viscous mucus. Due to this multifaceted role of HCO₃⁻ in the pancreas, its altered functioning can greatly contribute to the development of various exocrine diseases. It is well known that the exocrine and endocrine pancreas interact lively with each other, but not all details of this relationship are known. An interesting finding of a recent study by Jo-Watanabe et al. is that the G protein-coupled oestrogen receptor, GPR30, which is expressed in the endocrine pancreas, can be also activated by HCO₃⁻. This raises the possibility that ductal cells play a key role not only in the exocrine pancreas, but presumably also in endocrine function through HCO₃⁻ secretion.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"123 ","pages":"Article 102922"},"PeriodicalIF":4.3,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0143416024000800/pdfft?md5=915a16915870b0b0107a7b47ad293fd1&pid=1-s2.0-S0143416024000800-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141409228","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":"Genomic approachesidentifySTT4 as a new component in glucose-induced activation of yeast plasma membrane H+-ATPase","authors":"Patrícia Gonçalves Prates Barbosa ,&nbsp;Izinara Rosse ,&nbsp;Maria Ana Santana e Figueiredo Bessa ,&nbsp;Débora Faria Silva ,&nbsp;Margarete Alice Fontes Saraiva ,&nbsp;Aureliano Claret Cunha ,&nbsp;Lauro Moraes ,&nbsp;Bruna Trindade de Carvalho ,&nbsp;Maria R. Foulquié-Moreno ,&nbsp;Johan M. Thevelein ,&nbsp;Maria José Magalhães Trópia ,&nbsp;Ieso Miranda Castro ,&nbsp;Rogelio Lopes Brandão","doi":"10.1016/j.ceca.2024.102909","DOIUrl":"https://doi.org/10.1016/j.ceca.2024.102909","url":null,"abstract":"<div><p>Many studies have focused on identifying the signaling pathway by which addition of glucose triggers post-translational activation of the plasma membrane <em>H</em>⁺-ATPase in yeast. They have revealed that calcium signaling is involved in the regulatory pathway, supported for instance by the phenotype of mutants in<em>ARG82</em> that encodes an inositol kinase that phosphorylates inositol triphosphate (IP₃). Strong glucose-induced calcium signaling, and high glucose-induced plasma membrane <em>H</em>⁺-ATPase activation have been observed in a specific yeast strain with the PJ genetic background. In this study, we have applied pooled-segregant whole genome sequencing, QTL analysis and a new bioinformatics methodology for determining SNP frequencies to identify the cause of this discrepancy and possibly new components of the signaling pathway. This has led to the identification of an <em>STT4</em> allele with 6 missense mutations as a major causative allele, further supported by the observation that deletion of <em>STT4</em> in the inferior parent caused a similar increase in glucose-induced plasma membrane <em>H</em>⁺-ATPase activation. However, the effect on calcium signaling was different indicating the presence of additional relevant genetic differences between the superior and reference strains. Our results suggest that phosphatidylinositol-4-phosphate might play a role in the glucose-induced activation of plasma membrane <em>H</em>⁺-ATPase by controlling intracellular calcium release through the modulation of the activity of phospholipase C.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"123 ","pages":"Article 102909"},"PeriodicalIF":4.0,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141302457","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":"Interaction between TRP channels and anoctamins","authors":"Yasunori Takayama ,&nbsp;Makoto Tominaga","doi":"10.1016/j.ceca.2024.102912","DOIUrl":"10.1016/j.ceca.2024.102912","url":null,"abstract":"<div><p>Anoctamin 1 (ANO1) binds to transient receptor potential (TRP) channels (protein-protein interaction) and then is activated by TRP channels (functional interaction). TRP channels are non-selective cation channels that are expressed throughout the body and play roles in multiple physiological functions. Studies on TRP channels increased after the identification of TRP vanilloid 1 (TRPV1) in 1997. Calcium-activated chloride channel anoctamin 1 (ANO1, also called TMEM16A and DOG1) was identified in 2008. ANO1 plays a major role in TRP channel-mediated functions, as first shown in 2014 with the demonstration of a protein-protein interaction between TRPV4 and ANO1. In cells that co-express TRP channels and ANO1, calcium entering cells through activated TRP channels causes ANO1 activation. Therefore, in many tissues, the physiological functions related to TRP channels are modulated through chloride flux associated with ANO1 activation. In this review, we summarize the latest understanding of TRP-ANO1 interactions, particularly interaction of ANO1 with TRPV4, TRP canonical 6 (TRPC6), TRPV3, TRPV1, and TRPC2 in the salivary glands, blood vessels, skin keratinocytes, primary sensory neurons, and vomeronasal organs, respectively.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"121 ","pages":"Article 102912"},"PeriodicalIF":4.0,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0143416024000708/pdfft?md5=788b6fadfdeccc734c7d3f862606fd84&pid=1-s2.0-S0143416024000708-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141186526","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":"TMEM94 cannot be called a P-type ATPase","authors":"Michael Palmgren ,&nbsp;Jens Preben Morth ,&nbsp;Poul Nissen","doi":"10.1016/j.ceca.2024.102911","DOIUrl":"https://doi.org/10.1016/j.ceca.2024.102911","url":null,"abstract":"","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"123 ","pages":"Article 102911"},"PeriodicalIF":4.0,"publicationDate":"2024-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141328950","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}