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https://www.readbyqxmd.com/read/28220789/stim1-activates-crac-channels-through-rotation-of-the-pore-helix-to-open-a-hydrophobic-gate
#1
Megumi Yamashita, Priscilla S-W Yeung, Christopher E Ing, Beth A McNally, Régis Pomès, Murali Prakriya
Store-operated Ca(2+) release-activated Ca(2+) (CRAC) channels constitute a major pathway for Ca(2+) influx and mediate many essential signalling functions in animal cells, yet how they open remains elusive. Here, we investigate the gating mechanism of the human CRAC channel Orai1 by its activator, stromal interacting molecule 1 (STIM1). We find that two rings of pore-lining residues, V102 and F99, work together to form a hydrophobic gate. Mutations of these residues to polar amino acids produce channels with leaky gates that conduct ions in the resting state...
February 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28219928/mitochondria-control-store-operated-ca-2-entry-through-na-and-redox-signals
#2
Tsipi Ben-Kasus Nissim, Xuexin Zhang, Assaf Elazar, Soumitra Roy, Judith A Stolwijk, Yandong Zhou, Rajender K Motiani, Maxime Gueguinou, Nadine Hempel, Michal Hershfinkel, Donald L Gill, Mohamed Trebak, Israel Sekler
Mitochondria exert important control over plasma membrane (PM) Orai1 channels mediating store-operated Ca(2+) entry (SOCE). Although the sensing of endoplasmic reticulum (ER) Ca(2+) stores by STIM proteins and coupling to Orai1 channels is well understood, how mitochondria communicate with Orai1 channels to regulate SOCE activation remains elusive. Here, we reveal that SOCE is accompanied by a rise in cytosolic Na(+) that is critical in activating the mitochondrial Na(+)/Ca(2+) exchanger (NCLX) causing enhanced mitochondrial Na(+) uptake and Ca(2+) efflux...
February 20, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28218251/stim1-phosphorylation-at-y361-recruits-orai1-to-stim1-puncta-and-induces-ca-2-entry
#3
Pascal Yazbeck, Mohammad Tauseef, Kevin Kruse, Md-Ruhul Amin, Rayees Sheikh, Stefan Feske, Yulia Komarova, Dolly Mehta
Store-operated Ca(2+) entry (SOCE) mediates the increase in intracellular calcium (Ca(2+)) in endothelial cells (ECs) that regulates several EC functions including tissue-fluid homeostasis. Stromal-interaction molecule 1 (STIM1), upon sensing the depletion of (Ca(2+)) from the endoplasmic reticulum (ER) store, organizes as puncta that trigger store-operated Ca(2+) entry (SOCE) via plasmalemmal Ca(2+)-selective Orai1 channels. While the STIM1 and Orai1 binding interfaces have been mapped, signaling mechanisms activating STIM1 recruitment of Orai1 and STIM1-Orai1 interaction remains enigmatic...
February 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28209036/-primary-culture-and-functional-identification-of-distal-pulmonary-artery-smooth-muscle-cells-in-mice
#4
M C Li, Y Q Chen, C T Zhang, Q Jiang, W J Lu, J Wang
Objective: To establish a method of isolation and primary culture of mice distal pulmonary artery smooth muscle cells (PASMCs) and identify the functional properties. Methods: PASMCs were harvested from the distal pulmonary artery (PA) tissue of mice by enzymatic digestion of collagenaseⅠand papain; and the growth characteristics were observed under inverted microscope and identified by Immunofluorescence technique. Effects on the intracellular calcium ion concentration of distal PASMCs were detected by Fura-2-AM fluorescent probe tracer under a fluorescence microscope in Krebs solution containing clopiazonic acid (CPA) and nifedipin (Nif)...
February 12, 2017: Chinese Journal of Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/28196740/dpb162-ae-an-inhibitor-of-store-operated-ca-2-entry-can-deplete-the-endoplasmic-reticulum-ca-2-store
#5
Mart Bittremieux, Julia V Gerasimenko, Marleen Schuermans, Tomas Luyten, Eloise Stapleton, Kamil J Alzayady, Humbert De Smedt, David I Yule, Katsuhiko Mikoshiba, Peter Vangheluwe, Oleg V Gerasimenko, Jan B Parys, Geert Bultynck
Store-operated Ca(2+) entry (SOCE), an important Ca(2+) signaling pathway in non-excitable cells, regulates a variety of cellular functions. To study its physiological role, pharmacological tools, like 2-aminoethyl diphenylborinate (2-APB), are used to impact SOCE. 2-APB is one of the best characterized SOCE inhibitors. However, 2-APB also activates SOCE at lower concentrations, while it inhibits inositol 1,4,5-trisphosphate receptors (IP3Rs), sarco/endoplasmic reticulum Ca(2+)-ATPases (SERCAs) and other ion channels, like TRP channels...
February 1, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28185894/trpc1-and-trpc4-channels-functionally-interact-with-stim1l-to-promote-myogenesis-and-maintain-fast-repetitive-ca-2-release-in-human-myotubes
#6
Fabrice Antigny, Jessica Sabourin, Sophie Saüc, Laurent Bernheim, Stéphane Koenig, Maud Frieden
STIM1 and Orai1 are essential players of store-operated Ca(2+) entry (SOCE) in human skeletal muscle cells and are required for adult muscle differentiation. Besides these two proteins, TRPC (transient receptor potential canonical) channels and STIM1L (a longer STIM1 isoform) are also present on muscle cells. In the present study, we assessed the role of TRPC1, TRPC4 and STIM1L in SOCE, in the maintenance of repetitive Ca(2+) transients and in muscle differentiation. Knockdown of TRPC1 and TRPC4 reduced SOCE by about 50% and significantly delayed the onset of Ca(2+) entry, both effects similar to STIM1L invalidation...
February 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28183802/differential-effects-of-anoctamins-on-intracellular-calcium-signals
#7
Inês Cabrita, Roberta Benedetto, Ana Fonseca, Podchanart Wanitchakool, Lalida Sirianant, Boris V Skryabin, Laura K Schenk, Hermann Pavenstädt, Rainer Schreiber, Karl Kunzelmann
The Ca(2+) activated Cl(-) channel TMEM16A [anoctamin (ANO)1] is homologous to yeast Ist2 and has been shown to tether the cortical endoplasmic reticulum (ER) to the plasma membrane. We therefore examined whether ANO1 and other members of the ANO family affect intracellular Ca(2+) ([Ca(2+)]i) signals. It is shown that expression of ANO1 augments Ca(2+) store release upon stimulation of GPCRs, whereas knockdown of ANO1, or lack of Ano1 expression in Ano1(-/-) animals as shown in an earlier report, inhibits Ca(2+) release...
February 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28181236/ca-2-tunneling-through-the-er-lumen-as-a-mechanism-for-delivering-ca-2-entering-via-store-operated-ca-2-channels-to-specific-target-sites
#8
Ole H Petersen, Raphael Courjaret, Khaled Machaca
Ca(2+) signalling is perhaps the most universal and versatile mechanism regulating a wide range of cellular processes. Because of the many different calcium-binding proteins distributed throughout cells, signalling precision requires localized rises in the cytosolic Ca(2+) concentration. In electrically non-excitable cells, for example epithelial cells, this is achieved by primary release of Ca(2+) from the endoplasmic reticulum via Ca(2+) release channels placed close to the physiological target. Because any rise in the cytosolic Ca(2+) concentration activates Ca(2+) extrusion, and in order for cells not to run out of Ca(2+) , there is a need for compensatory Ca(2+) uptake from the extracellular fluid...
February 9, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28168659/btp2-a-store-operated-calcium-channel-inhibitor-attenuates-lung-ischemia-reperfusion-injury-in-rats
#9
Wei Zhang, Zeyou Qi, Yaping Wang
Lung ischemia-reperfusion (I/R) injury is a critical complication following a lung transplant, cardiopulmonary bypass, pulmonary embolism, and trauma. Immune cells and their effector functions are involved in the lung I/R injury. Store-operated calcium channels (SOCC) are highly Ca(2+)-selective cation channels and have crucial effects on the immune system. It has been indicated that BTP2, a potent SOCC blocker, could inhibit pro-inflammatory cytokine production from immune cells both in vitro and in vivo. Therefore, this study was conducted to investigate the beneficial effects of BTP2 on lung I/R injury in Sprague-Dawley (SD) rats...
February 7, 2017: Inflammation
https://www.readbyqxmd.com/read/28164587/high-expression-of-orai1-enhances-cell-proliferation-and-is-associated-with-poor-prognosis-in-human-colorectal-cancer
#10
Lin Gui, Zhenjun Wang, Jiagang Han, Huachong Ma, Zhulin Li
BACKGROUND: Store-operated Ca2+ entry (SOCE) is the predominant Ca2+ influx mechanism in non-excitable cells and regulates a variety of cellular functions. As the essential channel pore-forming protein of SOCE, Orai1 has recently been implicated in carcinogenesis and tumor progression in multiple malignancies. However, the role of Orai1 in colorectal cancer (CRC) has not been investigated. METHODS: The expression of Orai1 in 21 CRC specimens was examined by immunohistochemistry (IHC) staining, Western blot, and qRT-PCR...
September 1, 2016: Clinical Laboratory
https://www.readbyqxmd.com/read/28155613/functional-upregulation-of-stim-1-orai-1-mediated-store-operated-ca2-contributing-to-the-hypertension-development-elicited-by-chronic-etoh-consumption
#11
Guilherme Henrique Souza Bomfim, Iago Méndez-López, Juan Alberto Arranz-Tagarro, Adriana Aparecida Ferraz Carbonel, Danilo Roman-Campos, Juan Fernando Padín, Antonio García García, Aron Jurkiewicz, Neide Hyppolito Jurkiewicz
Chronic ethanol (EtOH) consumption has been associated with deleterious effects on the cardiovascular system by abnormal calcium (Ca²⁺) handling. Store-operated Ca2+ entry (SOCE) is related to cardiovascular remodeling which leads to the hypertension development, and the coupling between STIM-1 (ER Ca2+ sensor) and Orai-1 (channel pore) is a key mechanism to control SOCE through of store-operated Ca2+ channels (SOCCs). However, the role of STIM-1/Orai-1-mediated SOCE and its cross-talk with EtOH-triggered vascular remodeling and hypertension remain poorly understood...
February 1, 2017: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/28154371/oxidative-stress-and-calcium-dysregulation-by-palmitate-in-type-2-diabetes
#12
REVIEW
Luong Dai Ly, Shanhua Xu, Seong-Kyung Choi, Chae-Myeong Ha, Themis Thoudam, Seung-Kuy Cha, Andreas Wiederkehr, Claes B Wollheim, In-Kyu Lee, Kyu-Sang Park
Free fatty acids (FFAs) are important substrates for mitochondrial oxidative metabolism and ATP synthesis but also cause serious stress to various tissues, contributing to the development of metabolic diseases. CD36 is a major mediator of cellular FFA uptake. Inside the cell, saturated FFAs are able to induce the production of cytosolic and mitochondrial reactive oxygen species (ROS), which can be prevented by co-exposure to unsaturated FFAs. There are close connections between oxidative stress and organellar Ca(2+) homeostasis...
February 3, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28151934/hepatitis-b-virus-modulates-store-operated-calcium-entry-to-enhance-viral-replication-in-primary-hepatocytes
#13
Jessica C Casciano, Nicholas J Duchemin, R Jason Lamontagne, Laura F Steel, Michael J Bouchard
Many viruses modulate calcium (Ca2+) signaling to create a cellular environment that is more permissive to viral replication, but for most viruses that regulate Ca2+ signaling, the mechanism underlying this regulation is not well understood. The hepatitis B virus (HBV) HBx protein modulates cytosolic Ca2+ levels to stimulate HBV replication in some liver cell lines. A chronic HBV infection is associated with life-threatening liver diseases, including hepatocellular carcinoma (HCC), and HBx modulation of cytosolic Ca2+ levels could have an important role in HBV pathogenesis...
2017: PloS One
https://www.readbyqxmd.com/read/28145580/sp-2-iminosugar-%C3%AE-glucosidase-inhibitor-1-c-octyl-2-oxa-3-oxocastanospermine-specifically-affected-breast-cancer-cell-migration-through-stim1-%C3%AE-1-integrin-and-fak-signaling-pathways
#14
Nahla Gueder, Ghada Allan, Marie-Sophie Telliez, Frédéric Hague, José M Garcia Fernandez, Elena M Sanchez-Fernandez, Carmen Ortiz-Mellet, Ahmed Ahidouch, Halima Ouadid-Ahidouch
Aberrant glycosylation changes on many glycoproteins are often related to cancer progression and metastasis. sp(2) -Iminosugar-type castanospermine analogues, inhibitors of α-glucosidases, have been reported to exhibit antitumor activity. However, their effects on cell migration and the underlying molecular mechanism are not fully understood. Here, we investigated the effect of the pseudo- C-octyl glycoside 2-oxa-3-oxocastanospermine derivatives (CO-OCS) on breast cancer cells (MCF-7 and MDA-MB-231 cells), and MCF-10A mammary normal cell lines...
February 1, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28138348/cholesterol-enrichment-impairs-capacitative-calcium-entry-enos-phosphorylation-shear-stress-induced-no-production
#15
Allison M Andrews, Tenderano T Muzorewa, Kelly A Zaccheo, Donald G Buerk, Dov Jaron, Kenneth A Barbee
Endothelial dysfunction, characterized by decreased production or availability of nitric oxide (NO), is widely believed to be the hallmark of early-stage atherosclerosis. In addition, hypercholesterolemia is considered a major risk factor for development of atherosclerosis and is associated with impaired flow-induced dilation. However, the mechanism by which elevated cholesterol levels leads to decreased production of NO is unclear. NO is released in response to shear stress and agonist-evoked changes in intracellular calcium...
February 2017: Cellular and Molecular Bioengineering
https://www.readbyqxmd.com/read/28132808/store-operated-ca-2-entry-controls-induction-of-lipolysis-and-the-transcriptional-reprogramming-to-lipid-metabolism
#16
Mate Maus, Mario Cuk, Bindi Patel, Jayson Lian, Mireille Ouimet, Ulrike Kaufmann, Jun Yang, Rita Horvath, Hue-Tran Hornig-Do, Zofia M Chrzanowska-Lightowlers, Kathryn J Moore, Ana Maria Cuervo, Stefan Feske
Ca(2+) signals were reported to control lipid homeostasis, but the Ca(2+) channels and pathways involved are largely unknown. Store-operated Ca(2+) entry (SOCE) is a ubiquitous Ca(2+) influx pathway regulated by stromal interaction molecule 1 (STIM1), STIM2, and the Ca(2+) channel ORAI1. We show that SOCE-deficient mice accumulate pathological amounts of lipid droplets in the liver, heart, and skeletal muscle. Cells from patients with loss-of-function mutations in STIM1 or ORAI1 show a similar phenotype, suggesting a cell-intrinsic role for SOCE in the regulation of lipid metabolism...
January 21, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28131984/crispr-cas-induced-mutants-identify-a-requirement-for-dstim-in-larval-dopaminergic-cells-of-drosophila-melanogaster
#17
Trayambak Pathak, Deepti Trivedi, Gaiti Hasan
Molecular components of store-operated calcium entry have been identified in the recent past and consist of the endoplasmic reticulum membrane resident calcium-sensor STIM and the plasma membrane localised calcium channel, Orai. The physiological function of STIM and Orai is best defined in vertebrate immune cells. However, genetic studies with RNAi strains in Drosophila suggest a role in neuronal development and function. We generated a CRISPR-Cas mediated deletion for the gene encoding STIM in Drosophila (dSTIM), which we demonstrate is larval lethal...
January 27, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28130783/the-trpm7-channel-kinase-regulates-store-operated-calcium-entry
#18
Malika Faouzi, Tatiana Kilch, F David Horgen, Andrea Fleig, Reinhold Penner
The Transient receptor potential melastatin 7 (TRPM7) is a protein that combines an ion channel with an intrinsic kinase domain, enabling it to modulate cellular functions either by conducting ions through the pore or by phosphorylating downstream proteins through its kinase domain. In this study we present Store-Operated Calcium Entry (SOCE) as a novel target of TRPM7 kinase activity. TRPM7-deficient chicken DT40 B lymphocytes exhibit a strongly impaired SOCE compared to wild type cells due to reduced Calcium Release Activated Calcium (CRAC) currents and independent of potassium channel regulation, membrane potential changes or changes in cell-cycle distribution...
January 28, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28130257/hydrogen-peroxide-is-a-critical-regulator-of-the-hypoxia-induced-alterations-of-store-operated-ca2-entry-into-rat-pulmonary-arterial-smooth-muscle-cells
#19
Taoxiang Chen, Xiaoya Xu, Zhao Zhao, Fangyu Zhao, Yimei Gao, Xiaohong Yan, Yu Wan
To investigate the association between store-operated Ca2+ entry (SOCE) and reactive oxygen species (ROS) during hypoxia, this study determined the changes of transient receptor potential canonical 1 (TRPC1) and Orai1, two candidate proteins for store-operated Ca2+ (SOC) channels and their gate regulator, stromal interaction molecule 1 (STIM1) in a hypoxic environment and their relationship with ROS in pulmonary arterial smooth muscle cells (PASMCs). Exposing to hypoxia, a transient Ca2+ spike and subsequent Ca2+ plateau of SOCE in PASMCs were intensified when TRPC1, STIM1 and Orai1 were upregulated...
January 27, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28126709/enhanced-store-operated-ca2-influx-and-orai1-expression-in-ventricular-fibroblasts-from-human-failing-heart
#20
Gracious R Ross, Tanvir Bajwa, Stacie Edwards, Larisa Emelyanova, Farhan Rizvi, Ekhson L Holmuhamedov, Paul Werner, Francis X Downey, A Jamil Tajik, Arshad Jahangir
Excessive cardiac fibrosis, characterized by increased collagen-rich extracellular matrix (ECM) deposition, is a major predisposing factor for mechanical and electrical dysfunction in heart failure (HF). The human ventricular fibroblast (hVF) remodeling mechanisms that cause excessive collagen deposition in HF are unclear, although reports suggest a role for [Ca(2+)]i in fibrosis. Therefore, we determined the association of differences in cellular Ca(2+) dynamics and collagen secretion/deposition between hVFs from failing and normal (control) hearts...
January 26, 2017: Biology Open
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