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https://www.readbyqxmd.com/read/27929067/the-stim1-binding-site-nexus-remotely-controls-orai1-channel-gating
#1
Yandong Zhou, Xiangyu Cai, Natalia A Loktionova, Xianming Wang, Robert M Nwokonko, Xizhuo Wang, Youjun Wang, Brad S Rothberg, Mohamed Trebak, Donald L Gill
The ubiquitously expressed Orai Ca(2+) channels are gated through a unique process of intermembrane coupling with the Ca(2+)-sensing STIM proteins. Despite the significance of Orai1-mediated Ca(2+) signals, how gating of Orai1 is triggered by STIM1 remains unknown. A widely held gating model invokes STIM1 binding directly to Orai1 pore-forming helix. Here we report that an Orai1 C-terminal STIM1-binding site, situated far from the N-terminal pore helix, alone provides the trigger that is necessary and sufficient for channel gating...
December 8, 2016: Nature Communications
https://www.readbyqxmd.com/read/27913208/the-functions-of-store-operated-calcium-channels
#2
REVIEW
James W Putney, Natacha Steinckwich-Besançon, Takuro Numaga-Tomita, Felicity M Davis, Pooja N Desai, Diane M D'Agostin, Shilan Wu, Gary S Bird
Store-operated calcium channels provide calcium signals to the cytoplasm of a wide variety of cell types. The basic components of this signaling mechanism include a mechanism for discharging Ca(2+) stores (commonly but not exclusively phospholipase C and inositol 1,4,5-trisphosphate), a sensor in the endoplasmic reticulum that also serves as an activator of the plasma membrane channel (STIM1 and STIM2), and the store-operated channel (Orai1, 2 or 3). The advent of mice genetically altered to reduce store-operated calcium entry globally or in specific cell types has provided important tools to understand the functions of these widely encountered channels in specific and clinically important physiological systems...
November 29, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27913207/overexpression-of-stim1-in-neurons-in-mouse-brain-improves-contextual-learning-and-impairs-long-term-depression
#3
Łukasz Majewski, Filip Maciąg, Paweł M Boguszewski, Iga Wasilewska, Grzegorz Wiera, Tomasz Wójtowicz, Jerzy Mozrzymas, Jacek Kuznicki
STIM1 is an endoplasmic reticulum calcium sensor that is involved in several processes in neurons, including store-operated calcium entry. STIM1 also inhibits voltage-gated calcium channels, such as Cav1.2 and Cav3.1, and is thus considered a multifunctional protein. The aim of this work was to investigate the ways in which transgenic neuronal overexpression of STIM1 in FVB/NJ mice affects animal behavior and the electrophysiological properties of neurons in acute hippocampal slices. We overexpressed STIM1 from the Thy1...
November 29, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27879676/calcium-dyshomeostasis-in-tubular-aggregate-myopathy
#4
REVIEW
Jong-Mok Lee, Satoru Noguchi
Calcium is a crucial mediator of cell signaling in skeletal muscles for basic cellular functions and specific functions, including contraction, fiber-type differentiation and energy production. The sarcoplasmic reticulum (SR) is an organelle that provides a large supply of intracellular Ca(2+) in myofibers. Upon excitation, it releases Ca(2+) into the cytosol, inducing contraction of myofibrils. During relaxation, it takes up cytosolic Ca(2+) to terminate the contraction. During exercise, Ca(2+) is cycled between the cytosol and the SR through a system by which the Ca(2+) pool in the SR is restored by uptake of extracellular Ca(2+) via a specific channel on the plasma membrane...
November 22, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27878958/inhibition-of-orai1-mediated-ca-2-entry-enhances-chemosensitivity-of-hepg2-hepatocarcinoma-cells-to-5-fluorouracil
#5
Bao-Dong Tang, Xin Xia, Xiao-Fei Lv, Bei-Xin Yu, Jia-Ni Yuan, Xiao-Yi Mai, Jin-Yan Shang, Jia-Guo Zhou, Si-Jia Liang, Rui-Ping Pang
Increasing evidence supports that activation of store-operated Ca(2+) entry (SOCE) is implicated in the chemoresistance of cancer cells subjected to chemotherapy. However, the molecular mechanisms underlying chemoresistance are not well understood. In this study, we aim to investigate whether 5-FU induces hepatocarcinoma cell death through regulating Ca(2+) -dependent autophagy. [Ca(2+) ]i was measured using fura2/AM dye. Protein expression was determined by Western blotting and immunohistochemistry. We found that 5-fluorouracil (5-FU) induced autophagic cell death in HepG2 hepatocarcinoma cells by inhibiting PI3K/AKT/mTOR pathway...
November 23, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27876257/tubular-aggregate-myopathy-with-features-of-stormorken-disease-due-to-a-new-stim1-mutation
#6
Jean-Baptiste Noury, Johann Böhm, Georges Arielle Peche, Lucie Guyant-Marechal, Anne-Laure Bedat-Millet, Léa Chiche, Robert-Yves Carlier, Edoardo Malfatti, Norma B Romero, Tanya Stojkovic
STIM1 is a reticular Ca(2+) sensor composed of a luminal and a cytosolic domain. Missense mutations in the luminal domain have been associated with tubular aggregate myopathy (TAM), while cytosolic mutations can cause Stormorken syndrome, a multisystemic disease associating TAM with asplenia, thrombocytopenia, miosis, ichthyosis, short stature and dyslexia. Here we present the case of a 41-year-old female complaining of exercise intolerance. Clinical examination showed short stature, scoliosis, proximal muscle weakness with lower limb predominance, and ophthalmoplegia...
October 14, 2016: Neuromuscular Disorders: NMD
https://www.readbyqxmd.com/read/27868128/the-role-of-stim1-in-the-cr-vi-induced-ca-2-i-increase-and-cell-injury-in-l-02-hepatocytes
#7
Xing Yi, Yujing Zhang, Caigao Zhong, Xiali Zhong, Fang Xiao
Hexavalent chromium [Cr(vi)] is a potent cytotoxin and carcinogen. In recent years, drinking water contamination with Cr(vi) has become a worldwide problem of significant public health importance, thus much attention has been paid to the investigation of Cr(vi)-induced hepatotoxicity. The concentration of intracellular calcium ions ([Ca(2+)]i) was found to be increased after Cr(vi) exposure, but the exact underlying mechanisms involved in the Ca(2+) homeostasis imbalance remain poorly characterized. In the present study, by utilizing the antagonist of store-operated calcium channels (SOCCs) 2-aminoethoxydiphenyl borate (2-APB), small interfering RNA against stromal interaction molecule 1 (si-STIM1) and antioxidant N-acetylcysteine (NAC), we found that Cr(vi) induces [Ca(2+)]i increase, cell viability loss and transaminase (AST/ALT) leakage, and that these could be suppressed by both 2-APB and si-STIM1...
November 21, 2016: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/27866413/disbalance-of-calcium-regulation-related-genes-in-heart-of-broilers-induced-by-selenium-deficiency
#8
Ziwei Zhang, Man Liu, Zhenqiong Guan, Jie Yang, Zhonghua Liu, Shiwen Xu
Dietary selenium (Se) deficiency may influence the calcium (Ca) homeostasis in broilers. Our objective was to investigate the effects of Se deficiency on Ca regulation related genes' change in heart of broilers. In the present study, 1-day-old broilers were fed either a commercial diet (as control group) with 0.15 mg/kg Se or a Se-deficient diet (as L group) with 0.033 mg/kg Se for 35 days. We examined the mRNA expression levels of 15 Ca regulation related genes (ITPR 1, ITPR 2, ITPR3, RyR2, RyR3, SERCA1s, SLC8A1, PMCA1, CACNA1S, TRPC1, TRPC3, STIM1, ORAI1, CaLM and CRT) in the heart of broilers...
November 21, 2016: Avian Pathology: Journal of the W.V.P.A
https://www.readbyqxmd.com/read/27865927/structural-perturbations-induced-by-asn131-and-asn171-glycosylation-converge-within-the-efsam-core-and-enhance-stromal-interaction-molecule-1-mediated-store-operated-calcium-entry
#9
Yoo Jung Choi, Yue Zhao, Moshmi Bhattacharya, Peter B Stathopulos
A major intracellular calcium (Ca(2+)) uptake pathway in both excitable and non-excitable eukaryotic cells is store-operated Ca(2+) entry (SOCE). SOCE is the process by which endoplasmic reticulum (ER)-stored Ca(2+) depletion leads to activation of plasma membrane Ca(2+) channels to provide a sustained increase in cytosolic Ca(2+) levels that mediate a plethora of physiological processes ranging from the immune response to platelet aggregation. Stromal interaction molecule-1 (STIM1) is the principal regulator of SOCE and responds to changes in ER stored Ca(2+) through luminal sensing machinery composed of EF-hand and SAM domains (EFSAM)...
November 17, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27863410/elevated-expression-of-stim1-is-involved-in-lung-tumorigenesis
#10
Yadong Wang, Haiyu Wang, Li Li, Jiangmin Li, Teng Pan, Ding Zhang, Haiyan Yang
This study aimed to address the potential role of STIM1 (stromal interaction molecule 1) in lung tumorigenesis. Colony formation in soft agar assay and tumorigenicity in nude mice assay were conducted. Western blot, immunohistochemistry and quantitative real-time polymerase chain reaction were used to measure the STIM1 expression. The distribution of cell cycle was detected by flow cytometry assay. Our results showed that the expression of STIM1 mRNA was significantly higher in human lung tumors than that in adjacent non-neoplastic lung tissues...
November 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27847114/selective-activation-of-distinct-orai-channels-by-stim1
#11
REVIEW
Trevor J Shuttleworth
No abstract text is available yet for this article.
November 4, 2016: Cell Calcium
https://www.readbyqxmd.com/read/27826230/ampa-receptors-are-involved-in-store-operated-calcium-entry-and-interact-with-stim-proteins-in-rat-primary-cortical-neurons
#12
Joanna Gruszczynska-Biegala, Maria Sladowska, Jacek Kuznicki
The process of store-operated calcium entry (SOCE) leads to refilling the endoplasmic reticulum (ER) with calcium ions (Ca(2+)) after their release into the cytoplasm. Interactions between (ER)-located Ca(2+) sensors (stromal interaction molecule 1 [STIM1] and STIM2) and plasma membrane-located Ca(2+) channel-forming protein (Orai1) underlie SOCE and are well described in non-excitable cells. In neurons, however, SOCE appears to be more complex because of the importance of Ca(2+) influx via voltage-gated or ionotropic receptor-operated Ca(2+) channels...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27826057/adenylyl-cyclase-5-links-changes-in-calcium-homeostasis-to-camp-dependent-cyst-growth-in-polycystic-liver-disease
#13
Carlo Spirli, Valeria Mariotti, Ambra Villani, Luca Fabris, Romina Fiorotto, Mario Strazzabosco
BACKGROUND/AIMS: Genetic defects in Polycystins -1 or -2 (PC1 or PC2) cause polycystic liver disease associated with ADPKD (PLD-ADPKD). Progressive cyst growth is sustained by a cAMP-dependent Ras/ERK/HIFα pathway leading to increased autocrine/paracrine VEGF-A signalling. In PC2-defective cholangiocytes, store-operated Ca(2+) entry (SOCE), intracellular and endoplasmic reticulum [Ca(2+)]ER levels are reduced, while cAMP production in response to [Ca(2+)]ER depletion is increased. We hypothesized that in PC2-defective cells, in response to [Ca(2+)]ER depletion, the Ca(2+)-inhibitable adenylyl-cyclases AC5 or AC6 are activated by the ER chaperon STIM1 resulting in cAMP/PKA-dependent Ras/ERK/HIFα pathway activation...
November 5, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/27806271/functional-analysis-of-orai1-concatemers-supports-a-hexameric-stoichiometry-for-the-crac-channel
#14
Michelle Yen, Ludmila A Lokteva, Richard S Lewis
Store-operated Ca(2+) entry occurs through the binding of the endoplasmic reticulum (ER) Ca(2+) sensor STIM1 to Orai1, the pore-forming subunit of the Ca(2+) release-activated Ca(2+) (CRAC) channel. Although the essential steps leading to channel opening have been described, fundamental questions remain, including the functional stoichiometry of the CRAC channel. The crystal structure of Drosophila Orai indicates a hexameric stoichiometry, while studies of linked Orai1 concatemers and single-molecule photobleaching suggest that channels assemble as tetramers...
November 1, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/27793015/trpc1-stim1-activation-modulates-transforming-growth-factor-%C3%AE-induced-epithelial-to-mesenchymal-transition
#15
Anne Schaar, Pramod Sukumaran, Yuyang Sun, Archana Dhasarathy, Brij B Singh
Activation of Epithelial-to-Mesenchymal Transition (EMT) is important for tumor metastasis. Although growth factors such as TGFβ and EGF have been shown to induce EMT in breast epithelial cells, the mechanism resulting in migration is not well understood. Herein, we provide evidence that Ca2+ entry into the cell, especially upon store-depletion, plays an important role in TGFβ-induced EMT by promoting cellular migration and potentially leading to metastasis. The increased migration by TGFβ in non-cancerous cells was due to the loss of E-cadherin along with a subsequent increase in N-cadherin levels...
October 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27791458/store-operated-calcium-entry-activated-autophagy-protects-epc-proliferation-via-the-camkk2-mtor-pathway-in-ox-ldl-exposure
#16
Jie Yang, Jie Yu, Dongdong Li, Sanjiu Yu, Jingbin Ke, Lianyou Wang, Yanwei Wang, Youzhu Qiu, Xubin Gao, Jihang Zhang, Lan Huang
Improving biological functions of endothelial progenitor cells (EPCs) is beneficial to maintaining endothelium homeostasis and promoting vascular re-endothelialization. Because macroautophagy/autophagy has been documented as a double-edged sword in cell functions, its effects on EPCs remain to be elucidated. This study was designed to explore the role and molecular mechanisms of store-operated calcium entry (SOCE)-activated autophagy in proliferation of EPCs under hypercholesterolemia. We employed oxidized low-density lipoprotein (ox-LDL) to mimic hypercholesterolemia in bone marrow-derived EPCs from rat...
October 28, 2016: Autophagy
https://www.readbyqxmd.com/read/27780862/the-orai1-store-operated-calcium-channel-functions-as-a-hexamer
#17
Xiangyu Cai, Yandong Zhou, Robert M Nwokonko, Natalia A Loktionova, Xianming Wang, Ping Xin, Mohamed Trebak, Youjun Wang, Donald L Gill
Orai channels mediate store-operated Ca2+ signals crucial in regulating transcription in many cell types, and implicated in numerous immunological and inflammatory disorders. Despite their central importance, controversy surrounds the basic subunit structure of Orai channels, several biochemical and biophysical studies suggesting a tetrameric structure yet crystallographic evidence indicating a hexamer. We systematically investigated the subunit configuration of the functional Orai1 channel, generating a series of tdTomato-tagged concatenated Orai1 channel constructs (dimers to hexamers) expressed in CRISPR-derived Orai1-knockout HEK cells, stably expressing STIM1-YFP...
October 25, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27759093/live-cell-imaging-of-er-pm-contact-architecture-by-a-novel-tirfm-approach-reveals-extension-of-junctions-in-response-to-store-operated-ca-2-entry
#18
Michael Poteser, Gerd Leitinger, Elisabeth Pritz, Dieter Platzer, Irene Frischauf, Christoph Romanin, Klaus Groschner
Nanometer-spaced appositions between endoplasmic reticulum and plasma membrane (ER-PM junctions) stabilized by membrane-joining protein complexes are critically involved in cellular Ca(2+)-handling and lipid trafficking. ER-PM junctional architecture and plasticity associated with inter-membrane communication are as yet barely understood. Here, we introduce a method to precisely characterize ER-PM junction morphology and dynamics with high temporal resolution and minimal disturbance of junctional intermembrane communication...
October 19, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27753099/crac-channel-gating-and-its-modulation-by-stim1-and-2-aminoethoxydiphenyl-borate
#19
Sher Ali, Tao Xu, Xiaolan Xu
Ca(2+) release-activated Ca(2+) (CRAC) channels play an essential role in the immune system. The pore-forming subunit, Orai1, is an important pharmacological target. Here, we summarize the recent discoveries on the structure-function relationship of Orai1, as well as its interaction with the native channel opener STIM1 and chemical modulator 2-aminoethoxydiphenyl borate (2-APB). We first introduce the critical structural elements of Orai1, which include a Ca(2+) accumulating region, ion selectivity filter, hydrophobic centre, basic region, extended transmembrane Orai1 N-terminal (ETON) region, transmembrane (TM) regions 2 and 3, P245 bend, (263) SHK(265) hinge linker and L273-L276 hydrophobic patch...
October 18, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27753095/store-operated-stim1-translocation-and-interaction-with-trpc1-at-the-plasma-membrane-stimulates-plc-activity-to-induce-channel-gating-in-vascular-smooth-muscle-cells
#20
Jian Shi, Francesc Miralles, Lutz Birnbaumer, William A Large, Anthony P Albert
In vascular smooth muscle cells (VSMCs), stimulation of TRPC1-based SOCs mediate Ca(2+) entry pathways which regulate contractility, proliferation and migration. It is therefore important to understand how these channels are activated. Studies have shown that stimulation of TRPC1-based SOCs requires Gαq/PLCβ1 activities and PKC phosphorylation, but it is unclear how store depletion stimulates this gating pathway. The present work examines this issue by focusing on the role of STIM1, an endo/sarcoplasmic reticulum Ca(2+) sensor...
October 18, 2016: Journal of Physiology
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