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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
Gergely Kovács, Zsuzsanna Környei, Krisztina Tóth, Mária Baranyi, János Brunner, Máté Neubrandt, Ádám Dénes, Beáta Sperlágh
The P2X7R protein, a P2 type purinergic receptor functioning as a non-selective cation channel, is expressed in different cell types of the central nervous system in several regions of the brain. The activation of the P2X7R protein by ATP modulates excitatory neurotransmission and contributes to microglial activation, apoptosis and neuron-glia communication. Zinc is an essential micronutrient that is highly concentrated in the synaptic vesicles of glutamatergic hippocampal neurons where free zinc ions released into the synaptic cleft alter glutamatergic signal transmission...
July 30, 2018: Cell Calcium
Tomasz Wegierski, Jacek Kuznicki
Store-operated calcium entry (SOCE) is the flow of calcium ions (Ca2+ ) into cells in response to the depletion of intracellular Ca2+ stores that reside predominantly in the endoplasmic reticulum (ER). The role of SOCE has been relatively well understood for non-excitable cells. It is mediated mostly by the ER Ca2+ sensor STIM1 and plasma membrane Ca2+ channel Orai1 and serves to sustain Ca2+ signaling and refill ER Ca2+ stores. In contrast, because of the complexity of Ca2+ influx mechanisms that are present in excitable cells, our knowledge about the function of neuronal SOCE (nSOCE) is still nascent...
July 7, 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
M Eckstein, R S Lacruz
Enamel mineralization relies on Ca2+ availability provided by Ca2+ release activated Ca2+ (CRAC) channels. CRAC channels are modulated by the endoplasmic reticulum Ca2+ sensor STIM1 which gates the pore subunit of the channel known as ORAI1, found the in plasma membrane, to enable sustained Ca2+ influx. Mutations in the STIM1 and ORAI1 genes result in CRAC channelopathy, an ensemble of diseases including immunodeficiency, muscular hypotonia, ectodermal dysplasia with defects in sweat gland function and abnormal enamel mineralization similar to amelogenesis imperfecta (AI)...
November 2018: Cell Calcium
Ali H Jalloul, Guohong Liu, Robert T Szerencsei, Paul P M Schnetkamp
K+ -dependent Na+ -Ca2+ exchangers (NCKXs) belong to Ca2+ /cation antiporter gene superfamily. NCKX proteins play an important role in Ca2+ homeostasis and are bi-directional plasma membrane Ca2+ -transporters which utilize the inward Na+ and outward K+ gradients to move Ca2+ ions into and out of the cytosol (4Na+ :1Ca2+  + 1 K+ ). In this study, we examined residues in the two regions with the highest degree of homology between the different NCKX isoforms (α-1 and α-2 repeats) to determine which residues are important for Ca2+ coordination...
September 2018: Cell Calcium
Stephen D Bird
No abstract text is available yet for this article.
September 2018: Cell Calcium
Yixiao Mei, James E Barrett, Huijuan Hu
Calcium release-activated calcium (CRAC) channels are unique among ion channels that are activated in response to depletion of intracellular calcium stores and are highly permeable to Ca2+ compared to other cations. CRAC channels mediate an important calcium signal for a wide variety of cell types and are well studied in the immune system. They have been implicated in a number of disorders such as immunodeficiency, musculosketal disorders and cancer. There is growing evidence showing that CRAC channels are expressed in the nervous system and are involved in pathological conditions including pain...
September 2018: Cell Calcium
Mary S Kim, Alexander V Maltsev, Oliver Monfredi, Larissa A Maltseva, Ashley Wirth, Maria Cristina Florio, Kenta Tsutsui, Daniel R Riordon, Sean P Parsons, Syevda Tagirova, Bruce D Ziman, Michael D Stern, Edward G Lakatta, Victor A Maltsev
Current understanding of how cardiac pacemaker cells operate is based mainly on studies in isolated single sinoatrial node cells (SANC), specifically those that rhythmically fire action potentials similar to the in vivo behavior of the intact sinoatrial node. However, only a small fraction of SANC exhibit rhythmic firing after isolation. Other SANC behaviors have not been studied. Here, for the first time, we studied all single cells isolated from the sinoatrial node of the guinea pig, including traditionally studied rhythmically firing cells ('rhythmic SANC'), dysrhythmically firing cells ('dysrhythmic SANC') and cells without any apparent spontaneous firing activity ('dormant SANC')...
September 2018: Cell Calcium
Silke B Chalmers, Gregory R Monteith
Cancer is a major cause of death. The diversity of cancer types and the propensity of cancers to acquire resistance to therapies, including new molecularly targeted and immune-based therapies, drives the search for new ways to understand cancer progression. The remodelling of calcium (Ca2+ ) signalling and the role of the Ca2+ signal in controlling key events in cancer cells such as proliferation, invasion and the acquisition of resistance to cell death pathways is well established. Most of the work defining such changes has focused on Ca2+ permeable Transient Receptor Potential (TRP) Channels and some voltage gated Ca2+ channels...
September 2018: Cell Calcium
Kenneth A Stauderman
Calcium release-activated calcium (CRAC) channels have been the target of drug discovery for many years. The identification of STIM and Orai proteins as key components of CRAC channels greatly facilitated this process because their co-expression in cell lines produced electrophysiological currents (ICRAC ) much larger than those in native cells, making it easier to confirm and characterize the effects of modulatory compounds. A driving force in the quest for CRAC channel drugs has been the immunocompromised phenotype displayed by humans and mice with null or loss-of-function mutations in STIM1 or Orai1, suggesting that CRAC channel inhibitors could be useful therapeutics for autoimmune or inflammatory conditions...
September 2018: Cell Calcium
Klaus Groschner, Oleksandra Tiapko
Canonical TRP channels (TRPCs) are a particularly enigmatic family of signaling molecules with multimodal sensing features, being involved in a wide range of biological functions. Until very recently, the main hurdle towards comprehensive mechanistic understanding of TRPC signaling has been the lack of structural information. This has changed early this year by several reports on TRPC architectures resolved by single particle cryo-EM analysis. These studies confirmed recently elaborated concepts on TRPC structure-function relations, and unveiled unanticipated features and complexity in the TRPC sensing machinery...
September 2018: Cell Calcium
Corbett T Berry, Michael J May, Bruce D Freedman
The central role of Ca2+ signaling in the development of functional immunity and tolerance is well established. These signals are initiated by antigen binding to cognate receptors on lymphocytes that trigger store operated Ca2+ entry (SOCE). The underlying mechanism of SOCE in lymphocytes involves TCR and BCR mediated activation of Stromal Interaction Molecule 1 and 2 (STIM1/2) molecules embedded in the ER membrane leading to their activation of Orai channels in the plasma membrane. STIM/Orai dependent Ca2+ signals guide key antigen induced lymphocyte development and function principally through direct regulation of Ca2+ dependent transcription factors...
September 2018: Cell Calcium
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