Cell calcium最新文献

{"title":"Two-pore channels (TPCs) acts as a hub for excitation-contraction coupling, metabolism and cardiac hypertrophy signalling","authors":"Antoine de Zélicourt ,&nbsp;Abdallah Fayssoil ,&nbsp;Arnaud Mansart ,&nbsp;Faouzi Zarrouki ,&nbsp;Ahmed Karoui ,&nbsp;Jérome Piquereau ,&nbsp;Florence Lefebvre ,&nbsp;Pascale Gerbaud ,&nbsp;Delphine Mika ,&nbsp;Mbarka Dakouane-Giudicelli ,&nbsp;Erwan Lanchec ,&nbsp;Miao Feng ,&nbsp;Véronique Leblais ,&nbsp;Régis Bobe ,&nbsp;Jean-Marie Launay ,&nbsp;Antony Galione ,&nbsp;Ana Maria Gomez ,&nbsp;Sabine de la Porte ,&nbsp;José-Manuel Cancela","doi":"10.1016/j.ceca.2023.102839","DOIUrl":"10.1016/j.ceca.2023.102839","url":null,"abstract":"<div><p>Ca²⁺ signaling is essential for cardiac contractility and excitability in heart function and remodeling. Intriguingly, little is known about the role of a new family of ion channels, the endo-lysosomal non-selective cation “two-pore channel” (TPCs) in heart function. Here we have used double TPC knock-out mice for the 1 and 2 isoforms of TPCs (<em>Tpcn1/2^−/−</em>) and evaluated their cardiac function. Doppler-echocardiography unveils altered left ventricular (LV) systolic function associated with a LV relaxation impairment. In cardiomyocytes isolated from <em>Tpcn1/2^−/-</em> mice, we observed a reduction in the contractile function with a decrease in the sarcoplasmic reticulum Ca²⁺ content and a reduced expression of various key proteins regulating Ca²⁺ stores, such as calsequestrin. We also found that two main regulators of the energy metabolism, AMP-activated protein kinase and mTOR, were down regulated. We found an increase in the expression of TPC1 and TPC2 in a model of transverse aortic constriction (TAC) mice and in chronically isoproterenol infused WT mice. In this last model, adaptive cardiac hypertrophy was reduced by Tpcn1/2 deletion. Here, we propose a central role for TPCs and lysosomes that could act as a hub integrating information from the excitation-contraction coupling mechanisms, cellular energy metabolism and hypertrophy signaling.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"117 ","pages":"Article 102839"},"PeriodicalIF":4.0,"publicationDate":"2023-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138685163","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 influx into astrocytes plays a pivotal role in inflammation-driven behaviors","authors":"Alfonso Martín-Peña,&nbsp;Malú Gámez Tansey","doi":"10.1016/j.ceca.2023.102838","DOIUrl":"10.1016/j.ceca.2023.102838","url":null,"abstract":"","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"117 ","pages":"Article 102838"},"PeriodicalIF":4.0,"publicationDate":"2023-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138536392","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":"TRPV2 inhibitor tranilast prevents atrial fibrillation in rat models of pulmonary hypertension","authors":"Tianxin Ye, Zhuonan Song, Yunping Zhou, Zhangchi Liu, Yi Yu, Fangcong Yu, Yanan Chu, Jiaran Shi, Longbo Wang, Cui Zhang, Xin Liu, Bo Yang, Jinxiu Yang, Xingxiang Wang","doi":"10.1016/j.ceca.2023.102840","DOIUrl":"https://doi.org/10.1016/j.ceca.2023.102840","url":null,"abstract":"","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"95 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139021036","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":"Aromatically stacking the odds in favour of increased ORAI1 activation.","authors":"P. Stathopulos, M. Ikura","doi":"10.1016/j.ceca.2023.102841","DOIUrl":"https://doi.org/10.1016/j.ceca.2023.102841","url":null,"abstract":"","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"72 4","pages":""},"PeriodicalIF":4.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139021157","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 Ca2+-signaling in the regulation of epigenetic mechanisms","authors":"Andrés Hernández-Oliveras,&nbsp;Angel Zarain-Herzberg","doi":"10.1016/j.ceca.2023.102836","DOIUrl":"10.1016/j.ceca.2023.102836","url":null,"abstract":"<div><p>Epigenetic mechanisms regulate multiple cell functions like gene expression and chromatin conformation and stability, and its misregulation could lead to several diseases including cancer. Epigenetic drugs are currently under investigation in a broad range of diseases, but the cellular processes involved in regulating epigenetic mechanisms are not fully understood. Calcium (Ca²⁺) signaling regulates several cellular mechanisms such as proliferation, gene expression, and metabolism, among others. Moreover, Ca²⁺ signaling is also involved in diseases such as neurological disorders, cardiac, and cancer. Evidence indicates that Ca²⁺ signaling and epigenetics are involved in the same cellular functions, which suggests a possible interplay between both mechanisms. Ca²⁺<span>-activated transcription factors regulate the recruitment of chromatin remodeling complexes into their target genes, and Ca</span>²⁺-sensing proteins modulate their activity and intracellular localization. Thus, Ca²⁺ signaling is an important regulator of epigenetic mechanisms. Moreover, Ca²⁺ signaling activates epigenetic mechanisms that in turn regulate genes involved in Ca²⁺ signaling, suggesting possible feedback between both mechanisms. The understanding of how epigenetics are regulated could lead to developing better therapeutical approaches.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"117 ","pages":"Article 102836"},"PeriodicalIF":4.0,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138290463","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":"Nanojunctions: Specificity of Ca2+ signaling requires nano-scale architecture of intracellular membrane contact sites","authors":"Nicola Fameli ,&nbsp;Cornelis van Breemen ,&nbsp;Klaus Groschner","doi":"10.1016/j.ceca.2023.102837","DOIUrl":"https://doi.org/10.1016/j.ceca.2023.102837","url":null,"abstract":"<div><p>Spatio-temporal definition of Ca²⁺ signals involves the assembly of signaling complexes within the nano-architecture of contact sites between the sarco/endoplasmic reticulum (SR/ER) and the plasma membrane (PM). While the requirement of precise spatial assembly and positioning of the junctional signaling elements is well documented, the role of the nano-scale membrane architecture itself, as an ion-reflecting confinement of the signalling unit, remains as yet elusive. Utilizing the Na⁺/Ca²⁺ Exchanger-1 / SR/ER Ca²⁺ ATPase-2-mediated ER Ca²⁺ refilling process as a junctional signalling paradigm, we provide here the first evidence for an indispensable cellular function of the junctional membrane architecture. Our stochastic modeling approach demonstrates that junctional ER Ca²⁺ refilling operates exclusively at nano-scale membrane spacing, with a strong inverse relationship between junctional width and signaling efficiency. Our model predicts a breakdown of junctional Ca²⁺ signaling with loss of reflecting membrane confinement. In addition we consider interactions between Ca²⁺ and the phospholipid membrane surface, which may support interfacial Ca²⁺ transport and promote receptor targeting. Alterations in the molecular and nano-scale membrane organization at organelle-PM contacts are suggested as a new concept in pathophysiology.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"117 ","pages":"Article 102837"},"PeriodicalIF":4.0,"publicationDate":"2023-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0143416023001483/pdfft?md5=cfc85bddc4ac01d6a5b5254777a31fe6&pid=1-s2.0-S0143416023001483-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138437787","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":"Development of chemical tools based on GSK-7975A to study store-operated calcium entry in cells","authors":"Dominic Tscherrig ,&nbsp;Rajesh Bhardwaj ,&nbsp;Daniel Biner ,&nbsp;Jan Dernič ,&nbsp;Daniela Ross-Kaschitza ,&nbsp;Christine Peinelt ,&nbsp;Matthias A. Hediger ,&nbsp;Martin Lochner","doi":"10.1016/j.ceca.2023.102834","DOIUrl":"https://doi.org/10.1016/j.ceca.2023.102834","url":null,"abstract":"<div><p>Many physiological functions, such as cell differentiation, proliferation, muscle contraction, neurotransmission and fertilisation, are regulated by changes of Ca²⁺ levels. The major Ca²⁺ store in cells is the endoplasmic reticulum (ER). Certain cellular processes induce ER store depletion, <em>e.g.</em> by activating IP₃ receptors, that in turn induces a store refilling process known as store-operated calcium entry (SOCE). This refilling process entails protein-protein interactions between Ca²⁺ sensing stromal interaction molecules (STIM) in the ER membrane and Orai proteins in the plasma membrane. Fully assembled STIM/Orai complexes then form highly selective Ca²⁺ channels called Ca²⁺ release-activated Ca²⁺ Channels (CRAC) through which Ca²⁺ ions flow into the cytosol and subsequently are pumped into the ER by the sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA). Abnormal SOCE has been associated with numerous human diseases and cancers, and therefore key players STIM and Orai have attracted significant therapeutic interest. Several potent experimental and clinical candidate compounds have been developed and have helped to study SOCE in various cell types. We have synthesized multiple novel small-molecule probes based on the known SOCE inhibitor GSK-7975A. Here we present GSK-7975A derivatives, which feature photo-caging, photo-crosslinking, biotin and clickable moieties, and also contain deuterium labels. Evaluation of these GSK-7975A probes using a fluorometric imaging plate reader (FLIPR)-Tetra-based Ca²⁺ imaging assay showed that most synthetic modifications did not have a detrimental impact on the SOCE inhibitory activity. The photo-caged GSK-7975A was also used in patch-clamp electrophysiology experiments. In summary, we have developed a number of active, GSK-7975A-based molecular probes that have interesting properties and therefore are useful experimental tools to study SOCE in various cells and settings.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"117 ","pages":"Article 102834"},"PeriodicalIF":4.0,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0143416023001458/pdfft?md5=85ddcb0e5d20c905e16fb3ce898763b4&pid=1-s2.0-S0143416023001458-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138438295","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":"CRACing the role of calcium signaling in ILC2s","authors":"Guido H. Falduto,&nbsp;Daniella M. Schwartz","doi":"10.1016/j.ceca.2023.102835","DOIUrl":"https://doi.org/10.1016/j.ceca.2023.102835","url":null,"abstract":"","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"117 ","pages":"Article 102835"},"PeriodicalIF":4.0,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136719491","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":"Allosteric changes in protein stability and dynamics as pathogenic mechanism for calmodulin variants not affecting Ca2+ coordinating residues","authors":"Christina Vallentin Holler ,&nbsp;Nina Møller Petersson ,&nbsp;Malene Brohus ,&nbsp;Miska Aleksanteri Niemelä ,&nbsp;Emil Drivsholm Iversen ,&nbsp;Michael Toft Overgaard ,&nbsp;Hideo Iwaï ,&nbsp;Reinhard Wimmer","doi":"10.1016/j.ceca.2023.102831","DOIUrl":"10.1016/j.ceca.2023.102831","url":null,"abstract":"<div><p>Mutations in the small, calcium-sensing, protein calmodulin cause cardiac arrhythmia and can ultimately prove lethal. Here, we report the impact of the G113R variant on the structure and dynamics of the calmodulin molecule, both in the presence and in the absence of calcium. We show that the mutation introduces minor changes into the structure of calmodulin and that it changes the thermostability and thus the degree of foldedness at human body temperature. The mutation also severely impacts the intramolecular mobility of calmodulin, especially in the apo form. Glycine 113 acts as an alpha-helical C-capping residue in both apo/ - and Ca²⁺/calmodulin, but its exchange to arginine has very different effects on the apo and Ca²⁺ forms. The majority of arrhythmogenic calmodulin variants identified affects residues in the Ca²⁺ coordinating loops of the two C-domain EF-Hands, causing a ‘direct impact on Ca²⁺ binding’. However, G113R lies outside a Ca²⁺ coordinating loop and acts differently and more similar to the previously characterized arrhythmogenic N53I. Therefore, we suggest that altered apo/CaM dynamics may be a novel general disease mechanism, defining low-calcium target affinity – or Ca²⁺ binding kinetics – critical for timely coordination of essential ion-channels in the excitation-contraction cycle.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"117 ","pages":"Article 102831"},"PeriodicalIF":4.0,"publicationDate":"2023-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0143416023001422/pdfft?md5=6c4bf437308112416ee1589a34a0536f&pid=1-s2.0-S0143416023001422-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135764128","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":"The interplay between associated proteins, redox state and Ca2+ in the intraluminal ER compartment regulates the IP3 receptor","authors":"Jan B. Parys,&nbsp;Fernanda O. Lemos","doi":"10.1016/j.ceca.2023.102823","DOIUrl":"https://doi.org/10.1016/j.ceca.2023.102823","url":null,"abstract":"<div><p>There have been in the last three decades repeated publications indicating that the inositol 1,4,5-trisphosphate receptor (IP₃R) is regulated not only by cytosolic Ca²⁺ but also by intraluminal Ca²⁺. Although most studies indicated that a decreasing intraluminal Ca²⁺ level led to an inhibition of the IP₃R, a number of publications reported exactly the opposite effect, i.e. an inhibition of the IP₃R by high intraluminal Ca²⁺ levels. Although intraluminal Ca²⁺-binding sites on the IP₃Rs were reported, a regulatory role for them was not demonstrated. It is also well known that the IP₃R is regulated by a vast array of associated proteins, but only relatively recently proteins were identified that can be linked to the regulation of the IP₃R by intraluminal Ca²⁺. The first to be reported was annexin A1 that is proposed to associate with the second intraluminal loop of the IP₃R at high intraluminal Ca²⁺ levels and to inhibit the IP₃R. More recently, ERdj5/PDIA19 reductase was described to reduce an intraluminal disulfide bridge of IP₃R1 only at low intraluminal Ca²⁺ levels and thereby to inhibit the IP₃R. Annexin A1 and ERdj5/PDIA19 can therefore explain most of the experimental results on the regulation of the IP₃R by intraluminal Ca²⁺. Further studies are needed to provide a fuller understanding of the regulation of the IP₃R from the intraluminal side. These findings underscore the importance of the state of the endoplasmic reticulum in the control of IP₃R activity.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"117 ","pages":"Article 102823"},"PeriodicalIF":4.0,"publicationDate":"2023-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134688843","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}