Cell calcium最新文献

{"title":"A novel probe to monitor lysosome-mitochondria contact sites opens up a new path to study neurodegenerative diseases","authors":"Mai Makino , Shuhei Nakamura","doi":"10.1016/j.ceca.2024.102887","DOIUrl":"https://doi.org/10.1016/j.ceca.2024.102887","url":null,"abstract":"","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"120 ","pages":"Article 102887"},"PeriodicalIF":4.0,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140536794","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":"TRPM7 in neurodevelopment and therapeutic prospects for neurodegenerative disease","authors":"Zhengwei Luo ,&nbsp;Xinyang Zhang ,&nbsp;Andrea Fleig ,&nbsp;Daniel Romo ,&nbsp;Kenneth G. Hull ,&nbsp;F. David Horgen ,&nbsp;Hong-Shuo Sun ,&nbsp;Zhong-Ping Feng","doi":"10.1016/j.ceca.2024.102886","DOIUrl":"https://doi.org/10.1016/j.ceca.2024.102886","url":null,"abstract":"<div><p>Neurodevelopment, a complex and highly regulated process, plays a foundational role in shaping the structure and function of the nervous system. The transient receptor potential melastatin 7 (TRPM7), a divalent cation channel with an α-kinase domain, mediates a wide range of cellular functions, including proliferation, migration, cell adhesion, and survival, all of which are essential processes in neurodevelopment. The global knockout of either TRPM7 or TRPM7-kinase is embryonically lethal, highlighting the crucial role of TRPM7 in development <em>in vivo</em>. Subsequent research further revealed that TRPM7 is indeed involved in various key processes throughout neurodevelopment, from maintaining pluripotency during embryogenesis to regulating gastrulation, neural tube closure, axonal outgrowth, synaptic density, and learning and memory. Moreover, a discrepancy in TRPM7 expression and/or function has been associated with neuropathological conditions, including ischemic stroke, Alzheimer's disease, and Parkinson's disease. Understanding the mechanisms of proper neurodevelopment may provide us with the knowledge required to develop therapeutic interventions that can overcome the challenges of regeneration in CNS injuries and neurodegenerative diseases. Considering that ion channels are the third-largest class targeted for drug development, TRPM7′s dual roles in development and degeneration emphasize its therapeutic potential. This review provides a comprehensive overview of the current literature on TRPM7 in various aspects of neurodevelopment. It also discusses the links between neurodevelopment and neurodegeneration, and highlights TRPM7 as a potential therapeutic target for neurodegenerative disorders, with a focus on repair and regeneration.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"120 ","pages":"Article 102886"},"PeriodicalIF":4.0,"publicationDate":"2024-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140558195","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":"PDX1, a transcription factor essential for organ differentiation, regulates SERCA-dependent Ca2+ homeostasis in sensory neurons","authors":"Jami L. Saloman ,&nbsp;Ariel Y. Epouhe ,&nbsp;Catherine F. Ruff ,&nbsp;Kathryn M. Albers","doi":"10.1016/j.ceca.2024.102884","DOIUrl":"https://doi.org/10.1016/j.ceca.2024.102884","url":null,"abstract":"<div><p>Pancreatic and duodenal homeobox 1 (PDX1) is a transcription factor required for the development and differentiation of the pancreas. Previous studies indicated that PDX1 expression was restricted to the gastrointestinal tract. Using a cre-dependent reporter, we observed PDX1-dependent expression of tdtomato (PDX1-tom) in a subpopulation of sensory nerves. Many of these PDX1-tom afferents expressed the neurofilament 200 protein and projected to the skin. Tdtomato-labeled terminals were associated with hair follicles in the form of longitudinal and circumferential lanceolate endings suggesting a role in tactile and proprioceptive perception. To begin to examine the functional significance of PDX1 in afferents, we used Fura-2 imaging to examine calcium (Ca²⁺) handling under naïve and nerve injury conditions. Neuropathic injury is associated with increased intracellular Ca²⁺ signaling that in part results from dysregulation of the sarco/endoplasmic reticulum calcium transport ATPase (SERCA). Here we demonstrate that under naïve conditions, PDX1 regulates expression of the SERCA2B isoform in sensory neurons. In response to infraorbital nerve injury, a significant reduction of PDX1 and SERCA2B expression and dysregulation of Ca²⁺ handling occurs in PDX1-tom trigeminal ganglia neurons. The identification of PDX1 expression in the somatosensory system and its regulation of SERCA2B and Ca²⁺ handling provide a new mechanism to explain pathological changes in primary afferents that may contribute to pain associated with nerve injury.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"120 ","pages":"Article 102884"},"PeriodicalIF":4.0,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140341236","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":"Utilization of the genetically encoded calcium indicator Salsa6F in cardiac applications","authors":"Karla M. Márquez-Nogueras,&nbsp;Elisa Bovo,&nbsp;Jacy E. Neczypor,&nbsp;Quan Cao,&nbsp;Aleksey V. Zima,&nbsp;Ivana Y. Kuo","doi":"10.1016/j.ceca.2024.102873","DOIUrl":"10.1016/j.ceca.2024.102873","url":null,"abstract":"<div><p>Calcium signaling is a critical process required for cellular mechanisms such as cardiomyocyte contraction. The inability of the cell to properly activate or regulate calcium signaling can lead to contractile dysfunction. In isolated cardiomyocytes, calcium signaling has been primarily studied using calcium fluorescent dyes, however these dyes have limited applicability to whole organs. Here, we crossed the Salsa6f mouse which expresses a genetically encoded ratiometric cytosolic calcium indicator with a cardiomyocyte specific inducible cre to temporally-induce expression and studied cytosolic calcium transients in isolated cardiomyocytes and modified Langendorff heart preparations. Isolated cardiomyocytes expressing Salsa6f or Fluo-4AM loaded were compared. We also crossed the Salsa6f mouse with a floxed Polycystin 2 (PC2) mouse to test the feasibility of using the Salsa6f mouse to measure calcium transients in PC2 heterozygous or homozygous knock out mice. Although there are caveats in the applicability of the Salsa6f mouse, there are clear advantages to using the Salsa6f mouse to measure whole heart calcium signals.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"119 ","pages":"Article 102873"},"PeriodicalIF":4.0,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140272508","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":"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}