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Cell Calcium

Ralf Fliegert, Hans T Hölzer, Andreas H Guse
Transient receptor potential cation channel, subtype melastatin 2 (TRPM2), is important for several physiological functions, such as immune response or temperature regulation. Recently, the structure of full-length TRPM2 from zebrafish was published (Huang et al., 2018) proposing a new activation mechanism - is it really a paradigm shift or just reflects evolution of the channel?.
November 3, 2018: Cell Calcium
Christina K Go, Jonathan Soboloff
In a September 2018 paper published in Nature Communications, Gong et al. identified the domains through which human PMCA1 and neuroplastin (NPTN) interact. Upon binding, hPMCA1 TM domains separate T110 in TM1 and A370 in TM3 to reveal the Ca2+ -binding site. Thus, NPTN is able to directly modulate the accessibility of cytosolic Ca2+ to PMCA.
November 1, 2018: Cell Calcium
Antonio Michelucci, Maricela García-Castañeda, Simona Boncompagni, Robert T Dirksen
Store-operated Ca2+ entry (SOCE) is a Ca2+ entry mechanism activated by depletion of intracellular Ca2+ stores. In skeletal muscle, SOCE is mediated by an interaction between stromal-interacting molecule-1 (STIM1), the Ca2+ sensor of the sarcoplasmic reticulum, and ORAI1, the Ca2+ -release-activated-Ca2+ (CRAC) channel located in the transverse tubule membrane. This review focuses on the molecular mechanisms and physiological role of SOCE in skeletal muscle, as well as how alterations in STIM1/ORAI1-mediated SOCE contribute to muscle disease...
October 30, 2018: Cell Calcium
Jan B Parys
STAT3 is a pleiotropic prosurvival transcription factor with functions in nucleus and mitochondria. Avalle et al. (Cell Death Diff., 2018) now present evidence that STAT3 also promotes IP3 R3 degradation at the endoplasmic reticulum, thereby limiting Ca2+ transfer to the mitochondria and thus supporting cellular survival via an alternate pathway.
October 12, 2018: Cell Calcium
Thilini H Gamage, Gjermund Gunnes, Robert Hugh Lee, William Edward Louch, Asbjørn Holmgren, Joseph D Bruton, Emma Lengle, Terje R Selnes Kolstad, Tobias Revold, Silja Svanstrøm Amundsen, Knut Tomas Dalen, Pål Andre Holme, Geir Erland Tjønnfjord, Geir Christensen, Håkan Westerblad, Arne Klungland, Wolfgang Bergmeier, Doriana Misceo, Eirik Frengen
STIM1 and ORAI1 regulate store-operated Ca2+ entry (SOCE) in most cell types, and mutations in these proteins have deleterious and diverse effects. We established a mouse line expressing the STIM1 R304 W gain-of-function mutation causing Stormorken syndrome to explore effects on organ and cell physiology. While STIM1 R304 W was lethal in the homozygous state, surviving mice presented with reduced growth, skeletal muscle degeneration, and reduced exercise endurance. Variable STIM1 expression levels between tissues directly impacted cellular SOCE capacity...
October 5, 2018: Cell Calcium
Svetlana Sidorenko, Elizaveta Klimanova, Kseniya Milovanova, Olga D Lopina, Leonid V Kapilevich, Alexander V Chibalin, Sergei N Orlov
Elevation of Ca2+ i and AMP-activated protein kinase (AMPK) are considered as major signals triggering transcriptomic changes in exercising skeletal muscle. Electrical pulse stimulation (EPS) of cultured myotubes is widely employed as an in vitro model of muscle contraction. This study examines the impact of Ca2+ i -mediated and Ca2+ i -independent signaling in transcriptomic changes in EPS-treated C2C12 myotubes. Electrical pulse stimulation (40 V, 1 Hz, 10 ms, 2 h) resulted in [Ca2+ ]i oscillations, gain of Na+ i , loss of K+ i , and differential expression of 3215 transcripts...
September 30, 2018: Cell Calcium
Bin Liu, Wanxin Cao, Jiping Li, Jun Liu
Adenosine triphosphate (ATP) is stored as lysosomal vesicles in marginal cells of the stria vascular in neonatal rats, but the mechanisms of ATP release are unclear. Primary cultures of marginal cells from 1-day-old Sprague-Dawley rats were established. P2Y2 receptor and inositol 1,4,5-trisphosphate (IP3) receptor were immunolabelled in marginal cells of the stria vascular. We found that 30 μM ATP and 30 μM uridine triphosphate (UTP) evoked comparable significant increases in the intracellular Ca2+ concentration ([Ca2+ ]i ) in the absence of extracellular Ca2+ , whereas the response was suppressed by 100 μM suramin, 10 μM 1-(6-(17β-3-methoxyester-1,3,5(10)-trien-17-yl)amino)-hexyl)-1H-pyrrole-2,5-dione(U-73122), 100 μM 2-aminoethoxydiphenyl borate (2-APB) and 5 μM thapsigargin (TG), thus indicating that ATP coupled with the P2Y2 R-PLC-IP3 pathway to evoke Ca2+ release from the endoplasmic reticulum (ER)...
September 21, 2018: Cell Calcium
Paula Szalai, Jan B Parys, Geert Bultynck, Søren Brøgger Christensen, Poul Nissen, Jesper V Møller, Nikolai Engedal
Endoplasmic reticulum (ER) Ca2+ depletion activates the unfolded protein response (UPR), inhibits bulk autophagy and eventually induces cell death in mammalian cells. However, the extent and duration of ER Ca2+ depletion required is unknown. We instigated a detailed study in two different cell lines, using sarco/endoplasmic reticulum Ca2+ -ATPase (SERCA) inhibitors to gradually reduce ER Ca2+ levels in a controlled manner. Remarkably, UPR induction (as assessed by expression analyses of UPR-regulated proteins) and autophagy inhibition (as assessed by analyses of effects on starvation-induced bulk autophagy) required substantially higher drug concentrations than those needed to strongly decrease total ER Ca2+ levels...
September 17, 2018: Cell Calcium
Alasdair D Henry, N MacQuaide, F L Burton, A C Rankin, E G Rowan, R M Drummond
The pulmonary veins have an external sleeve of cardiomyocytes that are a widely recognised source of ectopic electrical activity that can lead to atrial fibrillation. Although the mechanisms behind this activity are currently unknown, changes in intracellular calcium (Ca2+ ) signalling are purported to play a role. Therefore, the intracellular Ca2+ concentration was monitored in the pulmonary vein using fluo-4 and epifluorescence microscopy. Electrical field stimulation evoked a synchronous rise in Ca2+ in neighbouring cardiomyocytes; asynchronous spontaneous Ca2+ transients between electrical stimuli were also present...
September 16, 2018: Cell Calcium
Liat van Dijk, Moshe Giladi, Bosmat Refaeli, Reuben Hiller, Mary Hongying Cheng, Ivet Bahar, Daniel Khananshvili
Prokaryotic and eukaryotic Na+ /Ca2+ exchangers (NCX) control Ca2+ homeostasis. NCX orthologs exhibit up to 104 -fold differences in their turnover rates (kcat ), whereas the ratios between the cytosolic (cyt) and extracellular (ext) Km values (Kint = Km Cyt /Km Ext ) are highly asymmetric and alike (Kint ≤ 0.1) among NCXs. The structural determinants controlling a huge divergence in kcat at comparable Kint remain unclear, although 11 (out of 12) ion-coordinating residues are highly conserved among NCXs. The crystal structure of the archaeal NCX (NCX_Mj) was explored for testing the mutational effects of pore-allied and loop residues on kcat and Kint ...
September 15, 2018: Cell Calcium
Patrick Toglia, Angelo Demuro, Don-On Daniel Mak, Ghanim Ullah
Intracellular accumulation of oligomeric forms of β amyloid (Aβ) are now believed to play a key role in the earliest phase of Alzheimer's disease (AD) as their rise correlates well with the early symptoms of the disease. Extensive evidence points to impaired neuronal Ca2+ homeostasis as a direct consequence of the intracellular Aβ oligomers. However, little is known about the downstream effects of the resulting Ca2+ rise on the many intracellular Ca2+ -dependent pathways. Here we use multiscale modeling in conjunction with patch-clamp electrophysiology of single inositol 1,4,5-trisphosphate (IP3 ) receptor (IP3 R) and fluorescence imaging of whole-cell Ca2+ response, induced by exogenously applied intracellular Aβ42 oligomers to show that Aβ42 inflicts cytotoxicity by impairing mitochondrial function...
September 12, 2018: Cell Calcium
Johann Böhm, Jocelyn Laporte
Calcium (Ca2+ ) is a key regulator for a large number of cellular functions in all kinds of cells, and small disturbances of Ca2+ homeostasis can severely compromise normal physiology in various tissues and organs. A major mechanism controlling Ca2+ homeostasis is store-operated Ca2+ entry (SOCE), which relies on the concerted action of the reticular Ca2+ sensor STIM1 and the plasma membrane Ca2+ channel ORAI1. Gain-of-function mutations in the respective genes induce excessive Ca2+ entry, and cause tubular aggregate myopathy (TAM) and Stormorken syndrome...
September 3, 2018: Cell Calcium
Ayushi Vashisht, Jyoti Tanwar, Rajender K Motiani
Store Operated Ca2+ Entry (SOCE) mediated by Orai channels is a ubiquitous Ca2+ influx pathway that regulates several cellular functions. We have earlier reported that Orai3, the mammalian specific Orai1 homolog, plays a critical role in breast cancer progression. More recently, Orai3 was demonstrated to regulate prostate and lung tumorigenesis. Although the tumorigenic potential of Orai3 is associated with increase in its expression, the molecular machinery regulating its expression remains largely unexplored...
November 2018: Cell Calcium
Rajendra K Sharma, Sreejit Parameswaran
The proteins which bind to calmodulin in a Ca2+ -dependent and reversible manner are known as calmodulin-binding proteins. These proteins are involved in a multitude of processes in which Ca2+ and calmodulin play crucial roles. Our group elucidated the mechanism and importance of these proteins in normal and diseased conditions. Various calmodulin-binding proteins were discovered and purified from bovine tissue including a heat stable calmodulin-binding protein 70, calmodulin-dependent protein kinase VI and a high molecular weight calmodulin-binding protein (HMWCaMBP)...
November 2018: Cell Calcium
Nhung Thi Nguyen, Guolin Ma, Eena Lin, Brendan D'Souza, Ji Jing, Lian He, Yun Huang, Yubin Zhou
Store-operated Ca²+ entry (SOCE) constitutes a major Ca2+ influx pathway in mammals to regulate a myriad of physiological processes, including muscle contraction, synaptic transmission, gene expression, and metabolism. In non-excitable cells, the Ca²+ release-activated Ca²+ (CRAC) channel, composed of ORAI and stromal interaction molecules (STIM), constitutes a prototypical example of SOCE to mediate Ca2+ entry at specialized membrane contact sites (MCSs) between the endoplasmic reticulum (ER) and the plasma membrane (PM)...
November 2018: Cell Calcium
Sergei E Permyakov, Alisa A Vologzhannikova, Polina A Khorn, Marina P Shevelyova, Alexei S Kazakov, Victor I Emelyanenko, Alexander I Denesyuk, Konstantin Denessiouk, Vladimir N Uversky, Eugene A Permyakov
Recently we found two highly conserved structural motifs in the proteins of the EF-hand calcium binding protein family. These motifs provide a supporting scaffold for the Ca2+ binding loops and contribute to the hydrophobic core of the EF-hand domain. Each structural motif forms a cluster of three amino acids called cluster I ('black' cluster) and cluster II ('grey' cluster). Cluster I is much more conserved and mostly incorporates aromatic amino acids. In contrast, cluster II includes a mix of aromatic, hydrophobic, and polar amino acids...
November 2018: Cell Calcium
Noam Levaot, Michal Hershfinkel
Zinc is an essential micronutrient affecting many aspects of human health. Cellular Zn2+ homeostasis is critical for cell function and survival. Zn2+ , acting as a first or second messenger, triggers signaling pathways that mediate the physiological roles of Zn2+ . Transient changes in Zn2+ concentrations within the cell or in the extracellular region occur following its release from Zn2+ binding metallothioneins, its transport across membranes by the ZnT or ZIP transporters, or release of vesicular Zn2+ . These transients activate a distinct Zn2+ sensing receptor, ZnR/GPR39, or modulate numerous proteins and signaling pathways...
November 2018: Cell Calcium
Gihan S Gunaratne, Malcolm E Johns, Hallie M Hintz, Timothy F Walseth, Jonathan S Marchant
The Ca2+ mobilizing second messenger nicotinic acid adenine dinucleotide phosphate (NAADP) regulates intracellular trafficking events, including translocation of certain enveloped viruses through the endolysosomal system. Targeting NAADP-evoked Ca2+ signaling may therefore be an effective strategy for discovering novel antivirals as well as therapeutics for other disorders. To aid discovery of novel scaffolds that modulate NAADP-evoked Ca2+ signaling in human cells, we have investigated the potential of using the sea urchin egg homogenate system for a screening campaign...
November 2018: Cell Calcium
Gihan S Gunaratne, Yang Yang, Fang Li, Timothy F Walseth, Jonathan S Marchant
Middle East Respiratory Syndrome coronavirus (MERS-CoV) infections are associated with a significant mortality rate, and existing drugs show poor efficacy. Identifying novel targets/pathways required for MERS infectivity is therefore important for developing novel therapeutics. As an enveloped virus, translocation through the endolysosomal system provides one pathway for cellular entry of MERS-CoV. In this context, Ca2+ -permeable channels within the endolysosomal system regulate both the luminal environment and trafficking events, meriting investigation of their role in regulating processing and trafficking of MERS-CoV...
November 2018: Cell Calcium
Lyudmyla Borysova, Kim A Dora, Christopher J Garland, Theodor Burdyga
The role of vascular gap junctions in the conduction of intercellular Ca2+ and vasoconstriction along small resistance arteries is not entirely understood. Some depolarizing agents trigger conducted vasoconstriction while others only evoke a local depolarization. Here we use a novel technique to investigate the temporal and spatial relationship between intercellular Ca2+ signals generated by smooth muscle action potentials (APs) and vasoconstriction in mesenteric resistance arteries (MA). Pulses of exogenous KCl to depolarize the downstream end (T1) of a 3 mm long artery increased intracellular Ca2+ associated with vasoconstriction...
November 2018: Cell Calcium
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