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https://www.readbyqxmd.com/read/29780388/regulation-of-hematopoietic-cell-development-and-function-through-phosphoinositides
#1
REVIEW
Mila Elich, Karsten Sauer
One of the most paramount receptor-induced signal transduction mechanisms in hematopoietic cells is production of the lipid second messenger phosphatidylinositol(3,4,5)trisphosphate (PIP3 ) by class I phosphoinositide 3 kinases (PI3K). Defective PIP3 signaling impairs almost every aspect of hematopoiesis, including T cell development and function. Limiting PIP3 signaling is particularly important, because excessive PIP3 function in lymphocytes can transform them and cause blood cancers. Here, we review the key functions of PIP3 and related phosphoinositides in hematopoietic cells, with a special focus on those mechanisms dampening PIP3 production, turnover, or function...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29760086/mapping-the-functional-anatomy-of-orai1-transmembrane-domains-for-crac-channel-gating
#2
Priscilla S-W Yeung, Megumi Yamashita, Christopher E Ing, Régis Pomès, Douglas M Freymann, Murali Prakriya
Store-operated Orai1 channels are activated through a unique inside-out mechanism involving binding of the endoplasmic reticulum Ca2+ sensor STIM1 to cytoplasmic sites on Orai1. Although atomic-level details of Orai structure, including the pore and putative ligand binding domains, are resolved, how the gating signal is communicated to the pore and opens the gate is unknown. To address this issue, we used scanning mutagenesis to identify 15 residues in transmembrane domains (TMs) 1-4 whose perturbation activates Orai1 channels independently of STIM1...
May 14, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29758025/clca2-is-a-positive-regulator-of-store-operated-calcium-entry-and-tmem16a
#3
Aarushi Sharma, Grace Ramena, Yufang Yin, Louis Premkumar, Randolph C Elble
The Chloride Channel Accessory (CLCA) protein family was first characterized as regulators of calcium-activated chloride channel (CaCC) currents (ICaCC), but the mechanism has not been fully established. We hypothesized that CLCAs might regulate ICaCC by modulating intracellular calcium levels. In cells stably expressing human CLCA2 or vector, we found by calcium imaging that CLCA2 moderately enhanced intracellular-store release but dramatically increased store-operated entry of calcium upon cytosolic depletion...
2018: PloS One
https://www.readbyqxmd.com/read/29712850/distinct-gating-mechanism-of-soc-channel-involving-stim-orai-coupling-and-an-intramolecular-interaction-of-orai-in-caenorhabditis-elegans
#4
Kyu Min Kim, Tharaka Wijerathne, Jin-Hoe Hur, Uk Jung Kang, Ihn Hyeong Kim, Yeong Cheon Kweon, Ah Reum Lee, Su Ji Jeong, Sang Kwon Lee, Yoon Young Lee, Bo-Woong Sim, Jong-Hee Lee, Chunggi Baig, Sun-Uk Kim, Kyu-Tae Chang, Kyu Pil Lee, Chan Young Park
Store-operated calcium entry (SOCE), an important mechanism of Ca2+ signaling in a wide range of cell types, is mediated by stromal interaction molecule (STIM), which senses the depletion of endoplasmic reticulum Ca2+ stores and binds and activates Orai channels in the plasma membrane. This inside-out mechanism of Ca2+ signaling raises an interesting question about the evolution of SOCE: How did these two proteins existing in different cellular compartments evolve to interact with each other? We investigated the gating mechanism of Caenorhabditis elegans Orai channels...
April 30, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29698850/structural-elements-of-stromal-interaction-molecule-function
#5
REVIEW
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
https://www.readbyqxmd.com/read/29686200/resolving-species-delimitation-within-the-genus-bunopus-blanford-1874-squamata-gekkonidae-in-iran-using-dna-barcoding-approach
#6
Azar Khosravani, Eskandar Rastegar-Pouyani, Nasrullah Rastegar-Pouyani, Hamzeh Oraie, Theodore J Papenfuss
Mitochondrial COI sequences were used to investigate species delimitation within the genus Bunopus in Iran. A dataset with a final sequence length of 633 nucleotides including 100 specimens from 31 geographically distant localities across Iran were generated. The result demonstrated that two major clades with strong support can be identified within the genus Bunopus in Iran. Clade A includes Bunopus crassicaudus and two new entities, eastern populations (subclade A2,1) and Shahdad populations (subclade A2,2)...
December 19, 2017: Zootaxa
https://www.readbyqxmd.com/read/29684786/gram-marks-the-spot-for-stim-commentary-on-gram-domain-proteins-specialize-functionally-distinct-er-pm-contact-sites-in-human-cells
#7
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
https://www.readbyqxmd.com/read/29623030/on-the-role-of-store-operated-calcium-entry-in-acute-and-chronic-neurodegenerative-diseases
#8
REVIEW
Agnese Secondo, Giacinto Bagetta, Diana Amantea
In both excitable and non-excitable cells, calcium (Ca2+ ) signals are maintained by a highly integrated process involving store-operated Ca2+ entry (SOCE), namely the opening of plasma membrane (PM) Ca2+ channels following the release of Ca2+ from intracellular stores. Upon depletion of Ca2+ store, the stromal interaction molecule (STIM) senses Ca2+ level reduction and migrates from endoplasmic reticulum (ER)-like sites to the PM where it activates the channel proteins Orai and/or the transient receptor potential channels (TRPC) prompting Ca2+ refilling...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29618985/the-complex-role-of-store-operated-calcium-entry-pathways-and-related-proteins-in-the-function-of-cardiac-skeletal-and-vascular-smooth-muscle-cells
#9
REVIEW
Javier Avila-Medina, Isabel Mayoral-Gonzalez, Alejandro Dominguez-Rodriguez, Isabel Gallardo-Castillo, Juan Ribas, Antonio Ordoñez, Juan A Rosado, Tarik Smani
Cardiac, skeletal, and smooth muscle cells shared the common feature of contraction in response to different stimuli. Agonist-induced muscle's contraction is triggered by a cytosolic free Ca2+ concentration increase due to a rapid Ca2+ release from intracellular stores and a transmembrane Ca2+ influx, mainly through L-type Ca2+ channels. Compelling evidences have demonstrated that Ca2+ might also enter through other cationic channels such as Store-Operated Ca2+ Channels (SOCCs), involved in several physiological functions and pathological conditions...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29604961/deletion-of-orai2-augments-endogenous-crac-currents-and-degranulation-in-mast-cells-leading-to-enhanced-anaphylaxis
#10
Volodymyr Tsvilovskyy, Alejandra Solís-López, Dagmar Schumacher, Rebekka Medert, Axel Roers, Ulrich Kriebs, Marc Freichel
All three members of the Orai family of cation channels-Orai1, Orai2 and Orai3-are integral membrane proteins that can form store-operated Ca2+ channels resembling endogenous calcium release-activated channels (CRAC) in many aspects. Loss of function studies in human and murine models revealed many functions of Orai1 proteins not only for Ca2+ homeostasis, but also for cellular and systemic functions in many cell types. By contrast, the knowledge regarding the contribution of Orai2 and Orai3 proteins in these processes is sparse...
May 2018: Cell Calcium
https://www.readbyqxmd.com/read/29600712/molecular-dynamics-simulations-of-orai-reveal-how-the-third-transmembrane-segment-contributes-to-hydration-and-ca-2-selectivity-in-crac-channels
#11
Azadeh Alavizargar, Claudio Berti, Mohammad Reza Ejtehadi, Simone Furini
Calcium release-activated calcium (CRAC) channels open upon depletion of Ca2+ from the endoplasmic reticulum, and when open, they are permeable to a selective flux of calcium ions. The atomic structure of Orai, the pore domain of CRAC channels, from Drosophila Melanogaster has revealed many details about conduction and selectivity in this family of ion channels. However, it is still unclear how residues on the third transmembrane helix can affect the conduction properties of the channel. Here, Molecular Dynamics and Brownian Dynamics simulations were employed to analyse how a conserved glutamate residue on the third transmembrane helix (E262) contributes to selectivity...
March 30, 2018: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29581306/cross-linking-of-orai1-channels-by-stim-proteins
#12
Yandong Zhou, Robert M Nwokonko, Xiangyu Cai, Natalia A Loktionova, Raz Abdulqadir, Ping Xin, Barbara A Niemeyer, Youjun Wang, Mohamed Trebak, Donald L Gill
The transmembrane docking of endoplasmic reticulum (ER) Ca2+ -sensing STIM proteins with plasma membrane (PM) Orai Ca2+ channels is a critical but poorly understood step in Ca2+ signal generation. STIM1 protein dimers unfold to expose a discrete STIM-Orai activating region (SOAR1) that tethers and activates Orai1 channels within discrete ER-PM junctions. We reveal that each monomer within the SOAR dimer interacts independently with single Orai1 subunits to mediate cross-linking between Orai1 channels. Superresolution imaging and mobility measured by fluorescence recovery after photobleaching reveal that SOAR dimer cross-linking leads to substantial Orai1 channel clustering, resulting in increased efficacy and cooperativity of Orai1 channel function...
March 26, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29449621/polygonum-aviculare-l-extract-and-quercetin-attenuate-contraction-in-airway-smooth-muscle
#13
Xi Luo, Lu Xue, Hao Xu, Qing-Yang Zhao, Qian Wang, Yu-Shan She, Dun-An Zang, Jinhua Shen, Yong-Bo Peng, Ping Zhao, Meng-Fei Yu, Weiwei Chen, Li-Qun Ma, Shu Chen, Shanshan Chen, Xiangning Fu, Sheng Hu, Xiaowei Nie, Chenyou Shen, Chunbin Zou, Gangjian Qin, Jiapei Dai, Guangju Ji, Yunchao Su, Shen Hu, Jingyu Chen, Qing-Hua Liu
Because of the serious side effects of the currently used bronchodilators, new compounds with similar functions must be developed. We screened several herbs and found that Polygonum aviculare L. contains ingredients that inhibit the precontraction of mouse and human airway smooth muscle (ASM). High K+ -induced precontraction in ASM was completely inhibited by nifedipine, a selective blocker of L-type voltage-dependent Ca2+ channels (LVDCCs). However, nifedipine only partially reduced the precontraction induced by acetylcholine chloride (ACH)...
February 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29423078/molecular-mechanisms-of-calcium-signaling-in-the-modulation-of-small-intestinal-ion-transports-and-bicarbonate-secretion
#14
Xin Yang, Guorong Wen, Biguang Tuo, Fenglian Zhang, Hanxing Wan, Jialin He, Shiming Yang, Hui Dong
Background and Purpose: Although Ca2+ signaling may stimulate small intestinal ion secretion, little is known about its critical role and the molecular mechanisms of Ca2+ -mediated biological action. Key Results: Activation of muscarinic receptors by carbachol(CCh) stimulated mouse duodenal I sc , which was significantly inhibited in Ca2+ -free serosal solution and by several selective store-operated Ca2+ channels(SOC) blockers added to the serosal side of duodenal tissues...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29414068/rapid-nmr-scale-purification-of-15-n-13-c-isotope-labeled-recombinant-human-stim1-coiled-coil-fragments
#15
Petr Rathner, Michael Stadlbauer, Christoph Romanin, Marc Fahrner, Isabella Derler, Norbert Müller
We report a new NMR-scale purification procedure for two recombinant wild type fragments of the stromal interaction molecule 1 (STIM1). This protein acts as a calcium sensor in the endoplasmic reticulum (ER) and extends into the cytosol accumulating at ER - plasma membrane (PM) junctions upon calcium store depletion ultimately leading to activation of the Orai/CRAC channel. The functionally relevant cytosolic part of STIM1 consists of three coiled coil domains, which are mainly involved in intra- and inter-molecular homomeric interactions as well as coupling to and gating of CRAC channels...
June 2018: Protein Expression and Purification
https://www.readbyqxmd.com/read/29383731/ca-2-signalling-in-mouse-urethral-smooth-muscle-in-situ-role-of-ca-2-stores-and-ca-2-influx-mechanisms
#16
Bernard T Drumm, Benjamin E Rembetski, Caroline A Cobine, Salah A Baker, Gerard P Sergeant, Mark A Hollywood, Keith D Thornbury, Kenton M Sanders
KEY POINTS: Contraction of urethral smooth muscle cells (USMCs) contributes to urinary continence. Ca2+ signalling in USMCs was investigated in intact urethral muscles using a genetically encoded Ca2+ sensor, GCaMP3, expressed selectively in USMCs. USMCs were spontaneously active in situ, firing intracellular Ca2+ waves that were asynchronous at different sites within cells and between adjacent cells. Spontaneous Ca2+ waves in USMCs were myogenic but enhanced by adrenergic or purinergic agonists and decreased by nitric oxide...
April 15, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29351410/hypoxia-selectively-upregulates-cation-channels-and-increases-cytosolic-ca-2-in-pulmonary-but-not-coronary-arterial-smooth-muscle-cells
#17
Xi He, Shanshan Song, Ramon J Ayon, Angela Balisterieri, Stephen M Black, Ayako Makino, W Gil Wier, Wei-Jin Zang, Jason X-J Yuan
Ca2+ signaling, particularly the mechanism via store-operated Ca2+ entry (SOCE) and receptor-operated Ca2+ entry (ROCE), plays a critical role in the development of acute hypoxia-induced pulmonary vasoconstriction and chronic hypoxia-induced pulmonary hypertension. This study aimed to test the hypothesis that chronic hypoxia differentially regulates the expression of proteins that mediate SOCE and ROCE [stromal interacting molecule (STIM), Orai, and canonical transient receptor potential channel TRPC6] in pulmonary (PASMC) and coronary (CASMC) artery smooth muscle cells...
April 1, 2018: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29337674/a-study-on-blocking-store-operated-ca2-entry-in-pulmonary-arterial-smooth-muscle-cells-with-xyloketals-from-marine-fungi
#18
Jie-Bin Zhou, Ying-Ying Sun, Ying-Lin Zheng, Chu-Qin Yu, Hua-Qing Lin, Ji-Yan Pang
In this study, the effect of four xyloketals 1-4 on store-operated calcium entry (SOCE) was investigated in primary distal pulmonary arterial smooth muscle cells (PASMCs) isolated from mice. The results showed that xyloketal A (1), an unusual ketal with C-3 symmetry, exhibited strong SOCE blocking activity. Secretion of interleukin-8 (IL-8) was also inhibited by xyloketal A. The parallel artificial membrane permeability assay (PAMPA) of 1-4 suggested that these xyloketals penetrated easily through the cell membrane...
December 20, 2017: Acta Pharmaceutica
https://www.readbyqxmd.com/read/29326165/phosphorylation-mediated-structural-changes-within-the-soar-domain-of-stromal-interaction-molecule-1-enable-specific-activation-of-distinct-orai-channels
#19
Jill L Thompson, Yue Zhao, Peter B Stathopulos, Alan Grossfield, Trevor J Shuttleworth
Low-conductance, highly calcium-selective channels formed by the Orai proteins exist as store-operated CRAC channels and store-independent, arachidonic acid-activated ARC channels. Both are activated by stromal interaction molecule 1 (STIM1), but CRAC channels are activated by STIM1 located in the endoplasmic reticulum membrane, whereas ARC channels are activated by the minor plasma membrane-associated pool of STIM1. Critically, maximally activated CRAC channel and ARC channel currents are completely additive within the same cell, and their selective activation results in their ability to each induce distinct cellular responses...
March 2, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29323264/orai3-calcium-channel-and-resistance-to-chemotherapy-in-breast-cancer-cells-the-p53-connection
#20
Jessy Hasna, Frédéric Hague, Lise Rodat-Despoix, Dirk Geerts, Catherine Leroy, David Tulasne, Halima Ouadid-Ahidouch, Philippe Kischel
Orai proteins are highly selective calcium channels playing an important role in calcium entry. Orai3 channels are overexpressed in breast cancer (BC) tissues, and involved in their proliferation, cell cycle progression and survival. Herein, we sought to address the involvement of Orai3 in resistance to chemotherapeutic drugs. Using high-throughput approaches, we investigated major changes induced by Orai3 overexpression, including downstream signaling mechanisms involved in BC chemotherapy resistance. Resistance was dependent on external calcium presence and thus Orai3 functionality...
March 2018: Cell Death and Differentiation
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