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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...
April 27, 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...
April 22, 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...
April 20, 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...
April 18, 2018: Cell Calcium
Paula Nunes, Nicolas Demaurex
GRAM domain proteins were reported as novel ER-PM tethers defining specific membrane contact sites (MCS) subdomains. GRAMD2a pre-marks the sites occupied by STIM1 at MCS and its ablation impairs STIM1 translocation, but not store-operated Ca2+ entry. We discuss these apparently counterintuitive findings in the context of STIM/ORAI signaling at MCS.
April 18, 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...
April 15, 2018: Cell Calcium
Brett Boonen, Yeranddy A Alpizar, Alicia Sanchez, Alejandro López-Requena, Thomas Voets, Karel Talavera
Acute neurogenic inflammation and pain associated to bacterial infection have been traditionally ascribed to sensitization and activation of sensory nerve afferents secondary to immune cell stimulation. However, we recently showed that lipopolysaccharides (LPS) directly activate the Transient Receptor Potential channels TRPA1 in sensory neurons and TRPV4 in airway epithelial cells. Here we investigated whether LPS activates other sensory TRP channels expressed in sensory neurons. Using intracellular Ca2+ imaging and patch-clamp we determined the effects of LPS on recombinant TRPV1, TRPV2, TRPM3 and TRPM8, heterologously expressed in HEK293T cells...
April 14, 2018: Cell Calcium
Vasiliy I Vladimirov, Evgeni Yu Zernii, Viktoriia E Baksheeva, Hanna Wimberg, Alexey S Kazakov, Natalya K Tikhomirova, Ekaterina L Nemashkalova, Vladimir A Mitkevich, Andrey A Zamyatnin, Valery M Lipkin, Pavel P Philippov, Sergei E Permyakov, Ivan I Senin, Karl-W Koch, Dmitry V Zinchenko
Rod cell membranes contain cholesterol-rich detergent-resistant membrane (DRM) rafts, which accumulate visual cascade proteins as well as proteins involved in regulation of phototransduction such as rhodopsin kinase and guanylate cyclases. Caveolin-1 is the major integral component of DRMs, possessing scaffolding and regulatory activities towards various signaling proteins. In this study, photoreceptor Ca2+ -binding proteins recoverin, NCS1, GCAP1, and GCAP2, belonging to neuronal calcium sensor (NCS) family, were recognized as novel caveolin-1 interacting partners...
April 14, 2018: Cell Calcium
Mateus Fila Pecenin, Lucas Borges-Pereira, Julio Levano-Garcia, Alexandre Budu, Eduardo Alves, Katsuhiko Mikoshiba, Andrew Thomas, Celia R S Garcia
Inositol 1,4,5 trisphosphate (IP3 ) signaling plays a crucial role in a wide range of eukaryotic processes. In Plasmodium falciparum, IP3 elicits Ca2+ release from intracellular Ca2+ stores, even though no IP3 receptor homolog has been identified to date. The human host hormone melatonin plays a key role in entraining the P. falciparum life cycle in the intraerythrocytic stages, apparently through an IP3 -dependent Ca2+ signal. The melatonin-induced cytosolic Ca2+ ([Ca2+ ]cyt ) increase and malaria cell cycle can be blocked by the IP3 receptor blocker 2-aminoethyl diphenylborinate (2-APB)...
March 14, 2018: Cell Calcium
Cristina Pierro, Xuexin Zhang, Cynthia Kankeu, Mohamed Trebak, Martin D Bootman, H Llewelyn Roderick
The KRAS GTPase plays a fundamental role in transducing signals from plasma membrane growth factor receptors to downstream signalling pathways controlling cell proliferation, survival and migration. Activating KRAS mutations are found in 20% of all cancers and in up to 40% of colorectal cancers, where they contribute to dysregulation of cell processes underlying oncogenic transformation. Multiple KRAS-regulated cell functions are also influenced by changes in intracellular Ca2+ levels that are concurrently modified by receptor signalling pathways...
March 14, 2018: Cell Calcium
Ilari Pulli, Taru Lassila, Guoping Pan, Daoguang Yan, Vesa M Olkkonen, Kid Törnquist
Oxysterol-binding protein related-protein 5 and 8 (ORP5/8) localize to the membrane contact sites (MCS) of the endoplasmic reticulum (ER) and the mitochondria, as well as to the ER-plasma membrane (PM) MCS. The MCS are emerging as important regulators of cell signaling events, including calcium (Ca2+ ) signaling. ORP5/8 have been shown to interact with phosphatidylinositol-4,5-bisphosphate (PIP2 ) in the PM, and to modulate mitochondrial respiration and morphology. PIP2 is the direct precursor of inositol trisphosphate (IP3 ), a key second messenger responsible for Ca2+ -release from the intracellular Ca2+ stores...
March 13, 2018: Cell Calcium
Andra M Sterea, Shekoufeh Almasi, Yassine El Hiani
Lysosomes serve as the control centre for cellular clearance. These membrane-bound organelles receive biomolecules destined for degradation from intracellular and extracellular pathways; thus, facilitating the production of energy and shaping the fate of the cell. At the base of their functionality are the lysosomal ion channels which mediate the function of the lysosome through the modulation of ion influx and efflux. Ion channels form pores in the membrane of lysosomes and allow the passage of ions, a seemingly simple task which harbours the potential of overthrowing the cell's stability...
March 10, 2018: Cell Calcium
John J Bassett, Alice H L Bong, Ellen K Janke, Mélanie Robitaille, Sarah J Roberts-Thomson, Amelia A Peters, Gregory R Monteith
Alterations in Ca2+ signaling can regulate key cancer hallmarks such as proliferation, invasiveness and resistance to cell death. Changes in the regulation of intracellular Ca2+ and specific components of Ca2+ influx are a feature of several cancers and/or cancer subtypes, including the basal-like breast cancer subtype, which has a poor prognosis. The development of genetically encoded calcium indicators, such as GCaMP6, represents an opportunity to measure changes in intracellular free Ca2+ during processes relevant to breast cancer progression that occur over long periods (e...
March 2, 2018: Cell Calcium
Ashley A Martin, Janet E Richmond
Nicotinic acetylcholine receptors (nAChR) are present in many excitable tissues and are found both pre and post-synaptically. Through their non-specific cationic permeability, these nAChRs have excitatory roles in neurotransmission, neuromodulation, synaptic plasticity, and neuroprotection. Thus, nAChR mislocalization or functional deficits are associated with many neurological disease states. Therefore identifying the mechanisms that regulate nAChR expression and function will inform our understanding of normal as well as pathological physiological conditions and offer avenues for potential therapeutic advances...
February 24, 2018: Cell Calcium
Stephen D Bird
Mast cells in the peritoneal membrane (PM) may degranulate to release preformed inflammatory mediators including histamine which is capable of diffusing into the surrounding interstitium, modulating cells in their vicinity including, human peritoneal mesothelial cells (hPMC). The present study aimed to investigate the quorum intracellular calcium ([Ca2+ i ]) response to histamine compared to the membrane soluble ionophore, A23187, in adherent cultured hPMC. To examine [Ca2+ i ] handling, Fura - 2 loaded cells were exposed to histamine and A23187...
February 21, 2018: Cell Calcium
Jeroen Bijnens, Ludwig Missiaen, Geert Bultynck, Jan B Parys
Kawasaki disease is a multi-systemic vasculitis that generally occurs in children and that can lead to coronary artery lesions. Recent studies showed that Kawasaki disease has an important genetic component. In this review, we discuss the single-nucleotide polymorphisms in the genes encoding proteins with a role in intracellular Ca2+ signaling: inositol 1,4,5-trisphosphate 3-kinase C, caspase-3, the store-operated Ca2+ -entry channel ORAI1, the type-3 inositol 1,4,5-trisphosphate receptor, the Na+ /Ca2+ exchanger 1, and phospholipase Cß4 and Cß1...
May 2018: Cell Calcium
Van Tran, Michael C H Park, Christian Stricker
Fluorescent Ca2+ indicators are widely used to measure the intracellular Ca2+ concentration ([Ca2+ ]i ) in living cells, including neurons. By calibrating an indicator in solutions that mimic the main ionic constituents of the actual cytoplasm, [Ca2+ ]i can be determined from the measured fluorescence intensity. However, different studies have reported considerably different Ca2+ -binding affinities (Kd ) for the same indicator, even though they used calibrating solutions with similar compositions. In this paper, we present a method to accurately determine the Kd values of non-ratiometric Ca2+ indicators in solutions that mimicked a standard patch-clamp internal solution...
May 2018: Cell Calcium
Hyungsup Kim, Hyesu Kim, Jesun Lee, Byeongjun Lee, Hee-Ryang Kim, Jooyoung Jung, Mi-Ock Lee, Uhtaek Oh
Anoctamins (ANOs) are multifunctional membrane proteins that consist of 10 homologs. ANO1 (TMEM16A) and ANO2 (TMEM16B) are anion channels activated by intracellular calcium that meditate numerous physiological functions. ANO6 is a scramblase that redistributes phospholipids across the cell membrane. The other homologs are not well characterized. We found ANO9/TMEM16J is a cation channel activated by a cAMP-dependent protein kinase A (PKA). Intracellular cAMP-activated robust currents in whole cells expressing ANO9, which were inhibited by a PKA blocker...
May 2018: Cell Calcium
Bradley D Stewart, Caitlin E Scott, Thomas P McCoy, Guo Yin, Florin Despa, Sanda Despa, Peter M Kekenes-Huskey
Hyperamylinemia is a condition that accompanies obesity and precedes type II diabetes, and it is characterized by above-normal blood levels of amylin, the pancreas-derived peptide. Human amylin oligomerizes easily and can deposit in the pancreas [1], brain [2], and heart [3], where they have been associated with calcium dysregulation. In the heart, accumulating evidence suggests that human amylin oligomers form moderately cation-selective [4,5] channels that embed in the cell sarcolemma (SL). The oligomers increase membrane conductance in a concentration-dependent manner [5], which is correlated with elevated cytosolic Ca2+ ...
May 2018: Cell Calcium
Philippa Dale, Victoria Head, Mark R Dowling, Colin W Taylor
Intracellular Ca2+ and cAMP typically cause opposing effects on airway smooth muscle contraction. Receptors that stimulate these pathways are therapeutic targets in asthma and chronic obstructive pulmonary disease. However, the interactions between different G protein-coupled receptors (GPCRs) that evoke cAMP and Ca2+ signals in human bronchial airway smooth muscle cells (hBASMCs) are poorly understood. We measured Ca2+ signals in cultures of fluo-4-loaded hBASMCs alongside measurements of intracellular cAMP using mass spectrometry or [3 H]-adenine labeling...
May 2018: Cell Calcium
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