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https://www.readbyqxmd.com/read/28644055/regulation-of-transient-receptor-potential-melastatin-4-channel-by-sarcoplasmic-reticulum-inositol-triphosphate-receptors-role-in-human-detrusor-smooth-muscle-function
#1
Aaron Provence, Eric S Rovner, Georgi V Petkov
We recently reported key physiological roles for Ca(2+)-activated transient receptor potential melastatin 4 (TRPM4) channels in detrusor smooth muscle (DSM). However, the Ca(2+)-signaling mechanisms governing TRPM4 channel activity in human DSM cells are unexplored. As the TRPM4 channels are activated by Ca(2+), inositol 1,4,5-trisphosphate receptor (IP3R)-mediated Ca(2+) release from the sarcoplasmic reticulum represents a potential Ca(2+) source for TRPM4 channel activation. We used clinically-characterized human DSM tissues to investigate the molecular and functional interactions of the IP3Rs and TRPM4 channels...
June 23, 2017: Channels
https://www.readbyqxmd.com/read/28642246/modulation-of-endoplasmic-reticulum-stress-controls-cd4-t-cell-activation-and-anti-tumor-function
#2
Jessica E Thaxton, Caroline Wallace, Brian Riesenberg, Yongliang Zhang, Chrystal Paulos, Craig Beeson, Bei Liu, Zihai Li
The endoplasmic reticulum (ER) is an energy-sensing organelle with intimate ties to programming cell activation and metabolic fate. T-cell receptor (TCR) activation represents a form of acute cell stress and induces mobilization of ER Ca(2+) stores. The role of the ER in programming T-cell activation and metabolic fate remains largely undefined. Gp96 is an ER protein with functions as a molecular chaperone and Ca(2+) buffering protein. We hypothesized that the ER stress response may be important for CD4(+) T-cell activation and that gp96 may be integral to this process...
June 22, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28637808/dmt-efficiently-inhibits-hepatic-gluconeogenesis-involving-g%C3%AE-q-signaling-pathway
#3
Ting-Ting Zhou, Fei Ma, Xiao-Fan Shi, Xin Xu, Te Du, Xiao-Dan Guo, Gai-Hong Wang, Liang Yu, Vatcharin Rukachaisirikul, Li-Hong Hu, Jing Chen, Xu Shen
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease with complicated pathogenesis, and targeting gluconeogenesis inhibition is a promising strategy for anti-diabetic drug discovery. G protein-coupled receptors (GPCRs) are classified as distinct families by heterotrimeric G proteins, primarily including Gαs, Gαi and Gαq. Gαs-coupled GPCRs function potently in the regulation of hepatic gluconeogenesis through activating cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway, and Gαi-coupled GPCRs exhibit inhibitory effect on adenylyl cyclase and reduce intracellular cAMP level...
June 21, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28629579/role-of-soce-architects-stim-and-orai-proteins-in-cell-death
#4
REVIEW
Jyoti Tanwar, Rajender K Motiani
Calcium (Ca(2+)) signaling plays a critical role in regulating plethora of cellular functions including cell survival, proliferation and migration. The perturbations in cellular Ca(2+) homeostasis can lead to cell death either by activating autophagic pathways or through induction of apoptosis. Endoplasmic reticulum (ER) is the major storehouse of Ca(2+) within cells and a number of physiological agonists mediate ER Ca(2+) release by activating IP3 receptors (IP3R). This decrease in ER Ca(2+) levels is sensed by STIM, which physically interacts and activates plasma membrane Ca(2+) selective Orai channels...
June 9, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28620198/hydrogen-gas-protects-ip3rs-by-reducing-disulfide-bridges-in-human-keratinocytes-under-oxidative-stress
#5
Ching-Ying Wu, Wen-Li Hsu, Ming-Hsien Tsai, Jui-Lin Liang, Jian-He Lu, Chia-Jung Yen, Hsin-Su Yu, Mami Noda, Chi-Yu Lu, Chu-Huang Chen, Shian-Jang Yan, Tohru Yoshioka
Based on the oxidative stress theory, aging derives from the accumulation of oxidized proteins induced by reactive oxygen species (ROS) in the cytoplasm. Hydrogen peroxide (H2O2) elicits ROS that induces skin aging through oxidation of proteins, forming disulfide bridges with cysteine or methionine sulfhydryl groups. Decreased Ca(2+) signaling is observed in aged cells, probably secondary to the formation of disulfide bonds among Ca(2+) signaling-related proteins. Skin aging processes are modeled by treating keratinocytes with H2O2...
June 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28618351/structure-of-ip3r-channel-high-resolution-insights-from-cryo-em
#6
REVIEW
Mariah R Baker, Guizhen Fan, Irina I Serysheva
Inositol 1,4,5-trisphosphate receptors (IP3Rs) are ubiquitously expressed intracellular Ca(2+) channels and the major mediators of cellular Ca(2+) signals generated by the release of Ca(2+) ions from intracellular stores in response to a variety of extracellular stimuli. Despite established physiological significance and proven involvements of IP3R channels in many human diseases, detailed structural basis for signal detection by these ion channels and their gating remain obscure. Recently, single particle electron cryomicroscopy (cryo-EM) has yielded a long-awaited near-atomic resolution structure of the entire full-length type 1 IP3R...
June 12, 2017: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/28615414/loss-of-ip3-receptor-mediated-ca-2-release-in-mouse-b-cells-results-in-abnormal-b-cell-development-and-function
#7
Huayuan Tang, Hong Wang, Qingsong Lin, Feifei Fan, Fei Zhang, Xiaohong Peng, Xi Fang, Jie Liu, Kunfu Ouyang
Intracellular calcium (Ca(2+)) mobilization after engagement of the BCR has been proposed to play an important role in B cell development and function. BCR activation causes an initial Ca(2+) release from the endoplasmic reticulum that is mediated by inositol 1,4,5-trisphosphate receptor (IP3R) and then triggers store-operated Ca(2+) entry once endoplasmic reticulum Ca(2+) store is depleted. Store-operated Ca(2+) entry has been shown to regulate B cell function but is dispensable for B cell development. By contrast, the function of IP3R-mediated Ca(2+) release in B cells remains to be determined...
June 14, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28614300/pten-counteracts-fbxl2-to-promote-ip3r3-and-ca-2-mediated-apoptosis-limiting-tumour-growth
#8
Shafi Kuchay, Carlotta Giorgi, Daniele Simoneschi, Julia Pagan, Sonia Missiroli, Anita Saraf, Laurence Florens, Michael P Washburn, Ana Collazo-Lorduy, Mireia Castillo-Martin, Carlos Cordon-Cardo, Said M Sebti, Paolo Pinton, Michele Pagano
In response to environmental cues that promote IP3 (inositol 1,4,5-trisphosphate) generation, IP3 receptors (IP3Rs) located on the endoplasmic reticulum allow the 'quasisynaptical' feeding of calcium to the mitochondria to promote oxidative phosphorylation. However, persistent Ca(2+) release results in mitochondrial Ca(2+) overload and consequent apoptosis. Among the three mammalian IP3Rs, IP3R3 appears to be the major player in Ca(2+)-dependent apoptosis. Here we show that the F-box protein FBXL2 (the receptor subunit of one of 69 human SCF (SKP1, CUL1, F-box protein) ubiquitin ligase complexes) binds IP3R3 and targets it for ubiquitin-, p97- and proteasome-mediated degradation to limit Ca(2+) influx into mitochondria...
June 14, 2017: Nature
https://www.readbyqxmd.com/read/28570539/monitoring-er-sr-calcium-release-with-the-targeted-ca2-sensor-catcher
#9
Florence N Reddish, Cassandra L Miller, Rakshya Gorkhali, Jenny J Yang
Intracellular calcium (Ca(2+)) transients evoked by extracellular stimuli initiate a multitude of biological processes in living organisms. At the center of intracellular calcium release are the major intracellular calcium storage organelles, the endoplasmic reticulum (ER) and the more specialized sarcoplasmic reticulum (SR) in muscle cells. The dynamic release of calcium from these organelles is mediated by the ryanodine receptor (RyR) and the inositol 1,4,5-triphosphate receptor (IP3R) with refilling occurring through the sarco/endoplasmic reticulum calcium ATPase (SERCA) pump...
May 19, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28546857/chloroquine-inhibits-ca-2-permeable-ion-channels-mediated-ca-2-signaling-in-primary-b-lymphocytes
#10
Yi-Fan Wu, Ping Zhao, Xi Luo, Jin-Chao Xu, Lu Xue, Qi Zhou, Mingrui Xiong, Jinhua Shen, Yong-Bo Peng, Meng-Fei Yu, Weiwei Chen, Liqun Ma, Qing-Hua Liu
BACKGROUND: Chloroquine, a bitter tastant, inhibits Ca(2+) signaling, resulting in suppression of B cell activation; however, the inhibitory mechanism remains unclear. RESULTS: In this study, thapsigargin (TG), but not caffeine, induced sustained intracellular Ca(2+) increases in mouse splenic primary B lymphocytes, which were markedly inhibited by chloroquine. Under Ca(2+)-free conditions, TG elicited transient Ca(2+) increases, which additionally elevated upon the restoration of 2 mM Ca(2+)...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/28538151/mapping-interpuff-interval-distribution-to-the-properties-of-inositol-trisphosphate-receptors
#11
Pengxing Cao, Martin Falcke, James Sneyd
Tightly clustered inositol trisphosphate receptors (IP3Rs) control localized Ca(2+) liberation from the endoplasmic reticulum to generate repetitive Ca(2+) puffs. Distributions of the interpuff interval (IPI), i.e., the waiting time between successive puffs, are found to be well characterized by a probability density function involving only two parameters, λ and ξ, which represent the basal rate of puff generation and the recovery rate from refractoriness, respectively. However, how the two parameters depend on the kinetic parameters of single IP3Rs in a cluster is still unclear...
May 23, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28526746/region-specific-proteolysis-differentially-regulates-type-1-inositol-1-4-5-trisphosphate-receptor-activity
#12
Liwei Wang, Larry E Wagner, Kamil J Alzayady, David I Yule
The inositol 1,4,5 trisphosphate receptor (IP3R) is an intracellular Ca2+ release channel expressed predominately on the membranes of the endoplasmic reticulum. IP3R1 can be cleaved by caspase or calpain into at least two receptor fragments. However, the functional consequences of receptor fragmentation are poorly understood. Our previous work has demonstrated that IP3R1 channels, formed following either enzymatic fragmentation or expression of the corresponding complementary polypeptide chains, retain tetrameric architecture and are still activated by IP3 binding, despite the loss of peptide continuity...
May 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28506928/distinct-phosphodiesterase-5a-containing-compartments-allow-selective-regulation-of-cgmp-dependent-signalling-in-human-arterial-smooth-muscle-cells
#13
Lindsay S Wilson, Manhong Guo, M Bibiana Umana, Donald H Maurice
Cyclic GMP (cGMP) translates and integrates much of the information encoded by nitric oxide (NO(·)) and several natriuretic peptides, including the atrial natriuretic peptide (ANP). Previously, we reported that integration of a cGMP-specific cyclic nucleotide phosphodiesterase, namely phosphodiesterase 5A (PDE5A), into a protein kinase G (PKG)- and inositol-1,4,5-trisphosphate receptor (IP3R)-containing endoplasmic reticulum (ER) signalosome allows localized control of PDE5A activity and of PKG-dependent inhibition of IP3-mediated release of ER Ca(2+) in human platelets...
May 12, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28506443/endoplasmic-reticulum-resident-selenoproteins-as-regulators-of-calcium-signaling-and-homeostasis
#14
REVIEW
Matthew W Pitts, Peter R Hoffmann
The human selenoprotein family contains 25 members that share the common feature of containing the amino acid, selenocysteine (Sec). Seven selenoproteins are localized to the endoplasmic reticulum (ER) and exhibit different structural features contributing to a range of cellular functions. Some of these functions are either directly or indirectly related to calcium (Ca(2+)) flux or homeostasis. The presence of the unique Sec residue within these proteins allows some to exert oxidoreductase activity, while the function of the Sec in other ER selenoproteins remains unclear...
May 4, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28486663/ca2-signaling-machinery-is-present-at-intercellular-junctions-and-structures-associated-with-junction-turnover-in-rat-sertoli-cells
#15
Kevin Lyon, Arlo Adams, Matthew Piva, Parisa Asghari, Edwin D Moore, A Wayne Vogl
The endoplasmic reticulum (ER) is a prominent organelle in Sertoli cells. It is an integral component of unique adhesion junctions (ectoplasmic specializations-ESs) in this cell type, and is closely associated with structures termed tubulobulbar complexes (TBCs) that internalize intercellular junctions during sperm release and during the translocation of spermatocytes through the blood-testis barrier. A role for the ER in Ca2+ regulation at ESs and TBCs has been suspected, but evidence for this function has proved elusive...
May 8, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28473752/spontaneous-ca-2-influx-in-drosophila-pupal-neurons-is-modulated-by-ip3-receptor-function-and-influences-maturation-of-the-flight-circuit
#16
Sumita Chakraborty, Gaiti Hasan
Inositol 1,4,5-trisphosphate receptors (IP3R) are Ca(2+) channels on the neuronal endoplasmic reticulum (ER) membrane. They are gated by IP3, produced upon external stimulation and activation of G protein-coupled receptors on the plasma membrane (PM). IP3-mediated Ca(2+) release, and the resulting depletion of the ER store, triggers entry of extracellular Ca(2+) by store-operated Ca(2+) entry (SOCE). Mutations in IP3R attenuate SOCE. Compromised IP3R function and SOCE during pupal development of Drosophila leads to flight deficits and mimics suppression of neuronal activity during pupal or adult development...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28419336/ip3r-mediated-ca2-signals-govern-hematopoietic-and-cardiac-divergence-of-flk1-cells-via-the-calcineurin-nfatc3-etv2-pathway
#17
Yi-Jie Wang, Jijun Huang, Wenqiang Liu, Xiaochen Kou, Huayuan Tang, Hong Wang, Xiujian Yu, Shaorong Gao, Kunfu Ouyang, Huang-Tian Yang
Ca2+ signals participate in various cellular processes with spatial and temporal dynamics, among which, inositol 1,4,5-trisphosphate receptors (IP3Rs)-mediated Ca2+ signals are essential for early development. However, the underlying mechanisms of IP3R-regulated cell fate decision remain largely unknown. Here we report that IP3Rs are required for the hematopoietic and cardiac fate divergence of mouse embryonic stem cells (mESCs). Deletion of IP3Rs (IP3R-tKO) reduced Flk1+/PDGFRα- hematopoietic mesoderm, c-Kit+/CD41+ hematopoietic progenitor cell population, and the colony-forming unit activity, but increased cardiac progenitor markers as well as cardiomyocytes...
April 13, 2017: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/28417016/hmgb1-release-by-h2o2-induced-hepatocytes-is-regulated-through-calcium-overload-and-58-f-interference
#18
Pei Zhao, Tingjie Ye, Xiaofeng Yan, Xudong Hu, Ping Liu, Xiaoling Wang
HMGB1 is passively released by injured or dying cells and aggravates inflammatory processes. The release of HMGB1 and calcium overload have each been reported to be important mediators of H2O2-induced injury. However, a potential connection between these two processes remains to be elucidated. In the present study, we employed H2O2-induced hepatocytes to investigate how calcium overload takes place during cellular injury and how the extracellular release of HMGB1 is regulated by this overload. In addition, we investigated the use of 58-F, a flavanone extracted from Ophiopogon japonicus, as a potential therapeutic drug...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28416699/ip3-mediated-gating-mechanism-of-the-ip3-receptor-revealed-by-mutagenesis-and-x-ray-crystallography
#19
Kozo Hamada, Hideyuki Miyatake, Akiko Terauchi, Katsuhiko Mikoshiba
The inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) is an IP3-gated ion channel that releases calcium ions (Ca(2+)) from the endoplasmic reticulum. The IP3-binding sites in the large cytosolic domain are distant from the Ca(2+) conducting pore, and the allosteric mechanism of how IP3 opens the Ca(2+) channel remains elusive. Here, we identify a long-range gating mechanism uncovered by channel mutagenesis and X-ray crystallography of the large cytosolic domain of mouse type 1 IP3R in the absence and presence of IP3 Analyses of two distinct space group crystals uncovered an IP3-dependent global translocation of the curvature α-helical domain interfacing with the cytosolic and channel domains...
May 2, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28413728/mechanism-of-endothelial-nitric-oxide-synthase-phosphorylation-and-activation-by-tentacle-extract-from-the-jellyfish-cyanea-capillata
#20
Beilei Wang, Dan Liu, Chao Wang, Qianqian Wang, Hui Zhang, Guoyan Liu, Xia Tao, Liming Zhang
Our previous study demonstrated that tentacle extract (TE) from the jellyfish Cyanea capillata (C. capillata) could cause a weak relaxation response mediated by nitric oxide (NO) using isolated aorta rings. However, the intracellular mechanisms of TE-induced vasodilation remain unclear. Thus, this study was conducted to examine the role of TE on Akt/eNOS/NO and Ca(2+) signaling pathways in human umbilical vein endothelial cells (HUVECs). Our results showed that TE induced dose- and time-dependent increases of eNOS activity and NO production...
2017: PeerJ
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