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Cell Calcium

Neeharika Nemani, Santhanam Shanmughapriya, Muniswamy Madesh
Ca2+ flux across the inner mitochondrial membrane (IMM) regulates cellular bioenergetics, intra-cellular cytoplasmic Ca2+ signals, and various cell death pathways. Ca2+ entry into the mitochondria occurs due to the highly negative membrane potential (ΔΨm ) through a selective inward rectifying MCU channel. In addition to being regulated by various mitochondrial matrix resident proteins such as MICUs, MCUb, MCUR1 and EMRE, the channel is transcriptionally regulated by upstream Ca2+ cascade, post transnational modification and by divalent cations...
June 27, 2018: Cell Calcium
Ali H Jalloul, Shitian Cai, Robert T Szerencsei, Paul P M Schnetkamp
K+ -dependent Na+ -Ca2+ exchangers (NCKXs) play an important role in Ca2+ homeostasis in many tissues. NCKX proteins 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 carried out scanning mutagenesis of all the residues of the highly conserved α-1 and α-2 repeats of NCKX2 to identify residues important for K+ transport. These structural elements are thought to be critical for cation transport...
June 25, 2018: Cell Calcium
Elisa Durán, María Ángeles Montes, Imane Jemal, Rachel Satterfield, Samuel Young, Guillermo Álvarez de Toledo
Continuous neurotransmitter release is subjected to synaptic vesicle availability, which in turn depends on vesicle recycling and the traffic of vesicles between pools. We studied the role of Synaptotagmin-7 (Syt-7) in synaptic vesicle accessibility for release in hippocampal neurons in culture. Synaptic boutons from Syt-7 knockout (KO) mice displayed normal basal secretion with no alteration in the RRP size or the probability of release. However, stronger stimuli revealed an increase in the size of the reserve and resting vesicle pools in Syt-7 KO boutons compared with WT...
June 22, 2018: Cell Calcium
Anatoliy Maslyukov, Kaizhen Li, Xin Su, Yury Kovalchuk, Olga Garaschuk
Spontaneous neuronal activity and concomitant intracellular Ca2+ signaling are abundant during early perinatal development and are well known for their key role in neuronal proliferation, migration, differentiation and wiring. However, much less is known about the in vivo patterns of spontaneous Ca2+ signaling in immature adult-born cells. Here, by using two-photon Ca2+ imaging, we analyzed spontaneous in vivo Ca2+ signaling in adult-born juxtaglomerular cells of the mouse olfactory bulb over the time period of 5 weeks, from the day of their arrival in the glomerular layer till their stable integration into the preexisting neural network...
June 6, 2018: Cell Calcium
Arunkumar Renganathan Chandrika, Mathew Steephan, Rajeevkumar Raveendran Nair, Suma Priya Sudarsana Devi, Mantosh Kumar, Soumya Paul, Mayadevi Madhavan, Ramakrishnapillai V Omkumar
Cellular calcium signaling events are transient. Hence they are observed in real time using fluorescence imaging or electrophysiological methods that require sophisticated instrumentation and specialized skills. For high throughput assays simple and inexpensive techniques are desirable. Many calcium channels that serve as drug targets have subtypes arising from diverse subunit combinations. These need to be targeted selectively for achieving efficacy and for avoiding side effects in therapies. This in turn increases the number of calcium channels that act as drug targets...
June 1, 2018: Cell Calcium
Bo Hellman, Heléne Dansk, Eva Grapengiesser
Many cellular processes, including pulsatile release of insulin, are triggered by increase of cytoplasmic Ca2+ . This study examines how somatostatin affects glucose generation of cytoplasmic Ca2+ oscillations in mouse islets in absence and presence of tolbutamide blockade of the KATP channels. Ca2+ was measured with dual wavelength microflurometry in isolated islets loaded with the indicator Fura-2. Rise of glucose from 3 to 20 mM evoked introductory lowering of Ca2+ prolonged by activation of somatostatin receptors...
June 1, 2018: Cell Calcium
Charlotte M Thomas, David J Timson
The trematode Schistosoma mansoni is a causative agent of schistosomiasis, the second most common parasitic disease of humans after malaria. Calcium homeostasis and calcium-mediated signalling pathways are of particular interest in this species. The drug of choice for treating schistosomiasis, praziquantel, disrupts the regulation of calcium uptake and there is interest in exploiting calcium-mediated processes for future drug discovery. Calmodulin is a calcium sensing protein, present in most eukaryotes. It is a critical regulator of processes as diverse as muscle contraction, cell division and, partly through interaction with voltage-gated calcium channels, intra-cellular calcium concentrations...
May 17, 2018: Cell Calcium
Ka Cheung Tam, Eunus Ali, Jin Hua, Tim Chataway, Greg J Barritt
Ca2+ entry through store-operated Ca2+ channels (SOCs) in the plasma membrane (PM) of hepatocytes plays a central role in the hormonal regulation of liver metabolism. SOCs are composed of Orai1, the channel pore protein, and STIM1, the activator protein, and are regulated by hormones and reactive oxygen species (ROS). In addition to Orai1, STIM1 also interacts with several other intracellular proteins. Most previous studies of the cellular functions of Orai1 and STIM1 have employed immortalised cells in culture expressing ectopic proteins tagged with a fluorescent polypeptide such as GFP...
May 15, 2018: Cell Calcium
Florian Lang, Lisann Pelzl, Stefan Hauser, Andreas Hermann, Christos Stournaras, Ludger Schöls
The pore forming Ca2+ release activated Ca2+ channel (CRAC) isoforms ORAI1-3 and their regulators STIM1,2 accomplish store operated Ca2+ entry (SOCE). Activation of SOCE may lead to cytosolic Ca2+ oscillations, which in turn support cell proliferation and cell survival. ORAI/STIM and thus SOCE are upregulated by the serum and glucocorticoid inducible kinase SGK1, a kinase under powerful genomic regulation and activated by phosphorylation via the phosphoinositol-3-phosphate pathway. SGK1 enhances ORAI1 abundance partially by phosphorylation of Nedd4-2, an ubiquitin ligase priming the channel protein for degradation...
May 3, 2018: Cell Calcium
Robert Zorec
The focus of this special issue (SI) »Membrane Merger in Conventional and Unconventional Vesicle Secretion« is regulated exocytosis, a universally conserved mechanism, consisting of a merger between the vesicle and the plasma membranes. Although this process evolved with eukaryotic organisms some three billion years ago (Spang et al., 2015), the understanding of physiology and patobiology of this process, especially at elementary vesicle level, remains unclear. Exocytotic fusion consists of several stages, starting by vesicle delivery to the plasma membrane, initially establishing a very narrow and stable fusion pore, that can reversibly open and close several times before it can fully widen...
July 2018: Cell Calcium
Julia Przibilla, Sandeep Dembla, Oleksandr Rizun, Annette Lis, Martin Jung, Johannes Oberwinkler, Andreas Beck, Stephan E Philipp
TRPM3 proteins assemble to Ca2+ -permeable cation channels in the plasma membrane, which act as nociceptors of noxious heat and mediators of insulin and cytokine release. Here we show that TRPM3 channel activity is strongly dependent on intracellular Ca2+ . Conceivably, this effect is attributed to the Ca2+ binding protein calmodulin, which binds to TRPM3 in a Ca2+ -dependent manner. We identified five calmodulin binding sites within the amino terminus of TRPM3, which displayed different binding affinities in dependence of Ca2+ ...
July 2018: Cell Calcium
Helmut Plattner, Alexei Verkhratsky
The aim of the present article is to analyse the evolutionary links between protozoa and neuronal and neurosecretory cells. To this effect we employ functional and topological data available for ciliates, in particular for Paramecium. Of note, much less data are available for choanoflagellates, the progenitors of metazoans, which currently are in the focus of metazoan genomic data mining. Key molecular players are found from the base to the highest levels of eukaryote evolution, including neurones and neurosecretory cells...
July 2018: Cell Calcium
Emma McIvor, Stephen Coombes, Rüdiger Thul
The spatial organisation of Orai channels and SERCA pumps within ER-PM junctions is important for enhancing the versatility and specificity of sub-cellular Ca2+ signals generated during store operated Ca2+ entry (SOCE). In this paper, we present a novel three dimensional spatio-temporal model describing Ca2+ dynamics in the ER-PM junction and sub-PM ER during SOCE. We investigate the role of Orai channel and SERCA pump location to provide insights into how these components shape the Ca2+ signals generated and affect ER refilling...
July 2018: Cell Calcium
Jens Hammann, Davide Bassetti, Robin White, Heiko J Luhmann, Sergei Kirischuk
Oligodendrocytes in the CNS myelinate neuronal axons, facilitating rapid propagation of action potentials. Myelin basic protein (MBP) is an essential component of myelin and its absence results in severe hypomyelination. In oligodendrocyte lineage cell (OLC) monocultures MBP synthesis starts at DIV4. Ouabain (10 nM), a Na+ ,K+ -ATPase (NKA) blocker, stimulates MBP synthesis. As OLCs express the α2 isoform of NKA (α2-NKA) that has a high affinity for ouabain, we hypothesized that α2-NKA mediates this effect...
July 2018: Cell Calcium
Christopher P Baines, Manuel Gutiérrez-Aguilar
Mitochondria from different organisms can undergo a sudden process of inner membrane unselective leakiness to molecules known as the mitochondrial permeability transition (MPT). This process has been studied for nearly four decades and several proteins have been claimed to constitute, or at least regulate the usually inactive pore responsible for this transition. However, no protein candidate proposed as the actual pore-forming unit has passed rigorous gain- or loss-of-function genetic tests. Here we review evidence for -and against- putative channel-forming components of the MPT pore...
July 2018: Cell Calcium
Eric I Gruenstein, Donna J Schlemm, Mridula Bethi, Stephen J Keller
Live yeast cell derivative (LYCD) is a medicinal yeast extract that has been used in the treatment of burns, wounds and hemorrhoids for over 70 years. It has been shown to enhance the closure of skin wounds in diabetic mice by increasing inflammation, angiogenesis, formation of granulation tissue and epithelial migration. An active fraction of LYCD has been identified as a mixture of peptides ranging in size from 5 kDA to 17 kDA. Despite its widespread use over many years, understanding of the mechanism by which LYCD acts to effect tissue repair responses is very limited...
July 2018: Cell Calcium
Hua Wei, Xiao-Hua Zhang, Cassandra Clift, Naohiro Yamaguchi, Martin Morad
Type-2 ryanodine receptors (RyR2s) play a pivotal role in cardiac excitation-contraction coupling by releasing Ca2+ from sarcoplasmic reticulum (SR) via a Ca2+ -induced Ca2+ release (CICR) mechanism. Two strategies have been used to study the structure-function characteristics of RyR2 and its disease associated mutations: (1) heterologous cell expression of the recombinant mutant RyR2s, and (2) knock-in mouse models harboring RyR2 point mutations. Here, we establish an alternative approach where Ca2+ signaling aberrancy caused by the RyR2 mutation is studied in human cardiomyocytes with robust CICR mechanism...
July 2018: Cell Calcium
Vincenzo Lariccia, Salvatore Amoroso
Na+ /Ca2+ exchangers (NCX) mediate bidirectional Ca2+ fluxes across cell membranes and contribute to Ca2+ homeostasis in many cell types. Exchangers are regulated by gating reactions that depend on Na+ and Ca2+ binding to transport and regulatory sites. A Na+ i -dependent inactivation is prominent in all isoforms, whereas Ca2+ i -dependent regulation varies among isoforms. Here we characterize new details of NCX operation and describe differences and similarities between NCX3 and NCX1 regulation by intracellular Ca2+ and ATP...
July 2018: Cell Calcium
Matthew J Novello, Jinhui Zhu, Qingping Feng, Mitsuhiko Ikura, Peter B Stathopulos
Stromal interaction molecule (STIM)-1 and -2 are multi-domain, single-pass transmembrane proteins involved in sensing changes in compartmentalized calcium (Ca2+ ) levels and transducing this cellular signal to Orai1 channel proteins. Our understanding of the molecular mechanisms underlying STIM signaling has been dramatically improved through available X-ray crystal and solution NMR structures. This high-resolution structural data has revealed that intricate intramolecular and intermolecular protein-protein interactions are involved in converting STIMs from the quiescent to activation-competent states...
July 2018: Cell Calcium
Martin D Bootman, Sarah Allman, Katja Rietdorf, Geert Bultynck
The study of cellular Ca2+ signalling is indebted to Roger Tsien for the invention of fluorescent indicators that can be readily loaded into living cells and provide the means to measure cellular Ca2+ changes over long periods of time with sub-second resolution and microscopic precision. However, a recent study [1] reminds us that as useful as these tools are they need to be employed with caution as there can be off-target effects. This article summarises these recent findings within the wider context of confounding issues that can be encountered when using chemical and genetically-encoded Ca2+ indicators, and briefly discusses some approaches that may mitigate against misleading outcomes...
July 2018: Cell Calcium
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