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IP3 Receptor

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https://www.readbyqxmd.com/read/28526746/region-specific-proteolysis-differentially-regulates-type-1-inositol-1-4-5-trisphosphate-receptor-activity
#1
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
#2
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/28506554/selective-dopamine-receptor-4-activation-mediates-the-hippocampal-neuronal-calcium-response-via-ip3-and-ryanodine-receptors
#3
Ya-Li Wang, Jian-Gang Wang, Fang-Li Guo, Xia-Huan Gao, Dan-Dan Zhao, Lin Zhang, Jian-Zhi Wang, Cheng-Biao Lu
Intracellular calcium is a key factor in most cellular processes, including cell growth, differentiation, proliferation and neurotransmitter release. Dopamine (DA) mediates synaptic transmission by regulating the intracellular calcium content. It is not clear, however, which specific subunit of the DA receptor contributes to DA modulation of intracellular calcium content changes. Through the traditional technique of Fura-2 calcium imaging, this study demonstrated that the DA can induce transient calcium in cultured hippocampal neurons and that this response can be mimicked by a selective dopamine receptor 4 (DR4) agonist PD168077 (PD)...
May 12, 2017: Brain Research
https://www.readbyqxmd.com/read/28504276/targeted-calcium-influx-boosts-cytotoxic-t-lymphocyte-function-in-the-tumour-microenvironment
#4
Kyun-Do Kim, Seyeon Bae, Tara Capece, Hristina Nedelkovska, Rafael G de Rubio, Alan V Smrcka, Chang-Duk Jun, Woojin Jung, Byeonghak Park, Tae-Il Kim, Minsoo Kim
Adoptive cell transfer utilizing tumour-targeting cytotoxic T lymphocytes (CTLs) is one of the most effective immunotherapies against haematological malignancies, but significant clinical success has not yet been achieved in solid tumours due in part to the strong immunosuppressive tumour microenvironment. Here, we show that suppression of CTL killing by CD4(+)CD25(+)Foxp3(+) regulatory T cell (Treg) is in part mediated by TGFβ-induced inhibition of inositol trisphosphate (IP3) production, leading to a decrease in T cell receptor (TCR)-dependent intracellular Ca(2+) response...
May 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28495747/reticulon-3-dependent-er-pm-contact-sites-control-egfr-nonclathrin-endocytosis
#5
Giusi Caldieri, Elisa Barbieri, Gilda Nappo, Andrea Raimondi, Massimo Bonora, Alexia Conte, Lisette G G C Verhoef, Stefano Confalonieri, Maria Grazia Malabarba, Fabrizio Bianchi, Alessandro Cuomo, Tiziana Bonaldi, Emanuele Martini, Davide Mazza, Paolo Pinton, Carlo Tacchetti, Simona Polo, Pier Paolo Di Fiore, Sara Sigismund
The integration of endocytic routes is critical to regulate receptor signaling. A nonclathrin endocytic (NCE) pathway of the epidermal growth factor receptor (EGFR) is activated at high ligand concentrations and targets receptors to degradation, attenuating signaling. Here we performed an unbiased molecular characterization of EGFR-NCE. We identified NCE-specific regulators, including the endoplasmic reticulum (ER)-resident protein reticulon 3 (RTN3) and a specific cargo, CD147. RTN3 was critical for EGFR/CD147-NCE, promoting the creation of plasma membrane (PM)-ER contact sites that were required for the formation and/or maturation of NCE invaginations...
May 12, 2017: Science
https://www.readbyqxmd.com/read/28495615/a-novel-function-of-tlr4-in-mediating-the-immunomodulatory-effect-of-benzanthrone-an-environmental-pollutant
#6
Prachi Tewari, Payal Mandal, Ruchi Roy, Somya Asthana, Premendra D Dwivedi, Mukul Das, Anurag Tripathi
Our prior studies have reported that Benzanthrone (BA) manifests inflammatory responses in the spleen of Balb/c mice. The present investigation was carried out to study the impact of BA on macrophages, which are the primary scavenger cells in the body that act as a connecting link between innate and adaptive immunity. Parenteral administration of BA (daily for one week) to mice resulted in enhanced levels of nitric oxide (NO) and overexpression of inflammatory markers (COX-2, MMP-9 and PGE-2) in macrophages; however the level of MHC class-I and MHC class-II receptors were down regulated...
May 8, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28481020/activation-of-ryanodine-receptors-is-required-for-pka-mediated-downregulation-of-a-type-k-channels-in-rat-hippocampal-neurons
#7
Yoon-Sil Yang, Sang-Chan Jeon, Moon-Suk Kang, Seon-Hee Kim, Su-Yong Eun, Soo-Hee Jin, Sung-Cherl Jung
A-type K(+) channels (IA channels) contribute to learning and memory mechanisms by regulating neuronal excitabilities in the CNS, and their expression level is targeted by Ca(2+) influx via synaptic NMDA receptors (NMDARs) during long-term potentiation (LTP). However, it is not clear how local synaptic Ca(2+) changes induce IA downregulation throughout the neuron, extending from the active synapse to the soma. In this study, we tested if two major receptors of endoplasmic reticulum (ER), ryanodine (RyRs), and IP3 (IP3 R) receptors, are involved in Ca(2+) -mediated IA downregulation in cultured hippocampal neurons of rats...
May 8, 2017: Journal of Neuroscience Research
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
#8
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/28435065/influence-of-er-leak-on-resting-cytoplasmic-ca-2-and-receptor-mediated-ca-2-signalling-in-human-macrophage
#9
Janice A Layhadi, Samuel J Fountain
Mechanisms controlling endoplasmic reticulum (ER) Ca(2+) homeostasis are important regulators of resting cytoplasmic Ca(2+) concentration ([Ca(2+)]cyto) and receptor-mediated Ca(2+) signalling. Here we investigate channels responsible for ER Ca(2+) leak in THP-1 macrophage and human primary macrophage. In the absence of extracellular Ca(2+) we employ ionomycin action at the plasma membrane to stimulate ER Ca(2+) leak. Under these conditions ionomycin elevates [Ca(2+)]cyto revealing a Ca(2+) leak response which is abolished by thapsigargin...
April 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28424618/pharmacological-and-biochemical-characterization-of-tlqp-21-activation-of-a-binding-site-on-cho-cells
#10
Laura Molteni, Laura Rizzi, Elena Bresciani, Roberta Possenti, Pamela Petrocchi Passeri, Corrado Ghè, Giampiero Muccioli, Jean-Alain Fehrentz, Pascal Verdié, Jean Martinez, Robert J Omeljaniuk, Giuseppe Biagini, Anna Binda, Ilaria Rivolta, Vittorio Locatelli, Antonio Torsello
VGF is a propeptide of 617 amino acids expressed throughout the central and the peripheral nervous system. VGF and peptides derived from its processing have been found in dense core vesicles and are released from neuronal and neuroendocrine cells via the regulated secretory pathway. Among VGF-derived neuropeptides, TLQP-21 (VGF(556-576)) has raised a huge interest and is one of most studied. TLQP-21 is a multifunctional neuropeptide involved in the control of several physiological functions, potentially including energy homeostasis, pain modulation, stress responsiveness and reproduction...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28416699/ip3-mediated-gating-mechanism-of-the-ip3-receptor-revealed-by-mutagenesis-and-x-ray-crystallography
#11
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/28413806/ryanodine-and-ip3-receptor-mediated-calcium-signaling-play-a-pivotal-role-in-neurological-infrared-laser-modulation
#12
Gleb P Tolstykh, Cory A Olsovsky, Bennett L Ibey, Hope T Beier
Pulsed infrared (IR) laser energy has been shown to modulate neurological activity through both stimulation and inhibition of action potentials. While the mechanism(s) behind this phenomenon is (are) not completely understood, certain hypotheses suggest that the rise in temperature from IR exposure could activate temperature- or pressure-sensitive ion channels or create pores in the cellular outer membrane, allowing an influx of typically plasma-membrane-impermeant ions. Studies using fluorescent intensity-based calcium ion ([Formula: see text]) sensitive dyes show changes in [Formula: see text] levels after various IR stimulation parameters, which suggests that [Formula: see text] may originate from the external solution...
April 2017: Neurophotonics
https://www.readbyqxmd.com/read/28413728/mechanism-of-endothelial-nitric-oxide-synthase-phosphorylation-and-activation-by-tentacle-extract-from-the-jellyfish-cyanea-capillata
#13
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
https://www.readbyqxmd.com/read/28412354/role-of-gpr30-in-estrogen-induced-prostate-epithelial-apoptosis-and-benign-prostatic-hyperplasia
#14
Deng-Liang Yang, Jia-Wen Xu, Jian-Guo Zhu, Yi-Lin Zhang, Jian-Bang Xu, Qing Sun, Xiao-Nian Cao, Wu-Lin Zuo, Ruo-Shui Xu, Jie-Hong Huang, Fu-Neng Jiang, Yang-Jia Zhuo, Bai-Quan Xiao, Yun-Zhong Liu, Dong-Bo Yuan, Zhao-Lin Sun, Hui-Chan He, Zhao-Rong Lun, Wei-De Zhong, Wen-Liang Zhou
Several studies have implicated estrogen and the estrogen receptor (ER) in the pathogenesis of benign prostatic hyperplasia (BPH); however, the mechanism underlying this effect remains elusive. In the present study, we demonstrated that estrogen (17β-estradiol, or E2)-induced activation of the G protein-coupled receptor 30 (GPR30) triggered Ca(2+) release from the endoplasmic reticulum, increased the mitochondrial Ca(2+) concentration, and thus induced prostate epithelial cell (PEC) apoptosis. Both E2 and the GPR30-specific agonist G1 induced a transient intracellular Ca(2+) release in PECs via the phospholipase C (PLC)-inositol 1, 4, 5-triphosphate (IP3) pathway, and this was abolished by treatment with the GPR30 antagonist G15...
April 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28412247/activation-of-phospholipase-c-%C3%AE-1-and-translocation-of-phosphatidylinositol-3-4-5-trisphosphate-3-phosphatase-contribute-to-gl-v9-induced-apoptosis-in-human-gastric-cancer-cells
#15
Kai Zhao, Guojun Li, Yuyuan Yao, Yuxin Zhou, Zhiyu Li, Qinglong Guo, Na Lu
Gastric cancer is the most common type of tumor in developing countries and the fourth most frequently diagnosed cancer worldwide. Here, we demonstrated the apoptotic effects of GL-V9 on several human gastric cancer cells and selected MGC-803 cells to uncover the underlying mechanism. GL-V9 elevated Bax/Bcl-2 ratio, abated mitochondrial membrane potential and triggered the onset of apoptotic execution in MGC-803 cells. Our research revealed that CHOP silencing could not inhibit apoptosis, neither could it block Ca(2+) release, suggesting that GL-V9-induced apoptosis was independent of CHOP...
April 13, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28404545/doxepin-inhibits-gpvi-dependent-platelet-ca-2-signaling-and-collagen-dependent-thrombus-formation
#16
Sascha Geue, Britta Walker-Allgaier, Daniela Eißler, Roland Tegtmeyer, Malte Schaub, Florian Lang, Meinrad Gawaz, Oliver Borst, Patrick Münzer
Platelet adhesion, activation and aggregation are essential for primary haemostasis, but are also critically involved in the development of acute arterial thrombotic occlusion. Stimulation of the collagen receptor glyocoprotein VI (GPVI) leads to PLCγ-dependent IP3 production with subsequent platelet activation, due to increased intracellular calcium concentration ([Ca(2+)]i). Although it has been described that tricyclic antidepressants potentially impair platelet activation, nothing is hitherto known about potential effects of the tricyclic antidepressant doxepin on platelet Ca(2+) signaling and thrombus formation...
April 12, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28390800/ca-2-release-via-two-pore-channel-type-2-tpc2-is-required-for-slow-muscle-cell-myofibrillogenesis-and-myotomal-patterning-in-intact-zebrafish-embryos
#17
Jeffrey J Kelu, Sarah E Webb, John Parrington, Antony Galione, Andrew L Miller
We recently demonstrated a critical role for two-pore channel type 2 (TPC2)-mediated Ca(2+) release during the differentiation of slow (skeletal) muscle cells (SMC) in intact zebrafish embryos, via the introduction of a translational-blocking morpholino antisense oligonucleotide (MO). Here, we extend our study and demonstrate that knockdown of TPC2 with a non-overlapping splice-blocking MO, knockout of TPC2 (via the generation of a tpcn2(dhkz1a) mutant line of zebrafish using CRISPR/Cas9 gene-editing), or the pharmacological inhibition of TPC2 action with bafilomycin A1 or trans-ned-19, also lead to a significant attenuation of SMC differentiation, characterized by a disruption of SMC myofibrillogenesis and gross morphological changes in the trunk musculature...
April 6, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28365690/changes-in-ip3-receptor-expression-and-function-in-aortic-smooth-muscle-of-atherosclerotic-mice
#18
Marie-Ann Ewart, Azizah Ugusman, Anisha Vishwanath, Tarek A M Almabrouk, Husam Alganga, Omar J Katwan, Pavlina Hubanova, Susan Currie, Simon Kennedy
Peroxynitrite is an endothelium-independent vasodilator that induces relaxation via membrane hyperpolarization. The activation of IP3 receptors triggers the opening of potassium channels and hyperpolarization. Previously we found that relaxation to peroxynitrite was maintained during the development of atherosclerosis due to changes in the expression of calcium-regulatory proteins. In this study we investigated: (1) the mechanism of peroxynitrite-induced relaxation in the mouse aorta, (2) the effect of atherosclerosis on relaxation to peroxynitrite and other vasodilators, and (3) the effect of atherosclerosis on the expression and function of the IP3 receptor...
2017: Journal of Vascular Research
https://www.readbyqxmd.com/read/28356704/osmotic-regulation-of-nfat5-expression-in-rpe-cells-the-involvement-of-purinergic-receptor-signaling
#19
Margrit Hollborn, Sarah Fischer, Heidrun Kuhrt, Peter Wiedemann, Andreas Bringmann, Leon Kohen
PURPOSE: Systemic hypertension is a risk factor for age-related neovascular retinal diseases. The major condition that induces hypertension is the intake of dietary salt (NaCl) resulting in increased extracellular osmolarity. High extracellular NaCl was has been shown to induce angiogenic factor production in RPE cells, in part via the transcriptional activity of nuclear factor of activated T cell 5 (NFAT5). Here, we determined the signaling pathways that mediate the osmotic expression of the NFAT5 gene in RPE cells...
2017: Molecular Vision
https://www.readbyqxmd.com/read/28348216/splicing-variation-of-long-irbit-determines-the-target-selectivity-of-irbit-family-proteins
#20
Katsuhiro Kawaai, Hideaki Ando, Nobuhiko Satoh, Hideomi Yamada, Naoko Ogawa, Matsumi Hirose, Akihiro Mizutani, Benjamin Bonneau, George Seki, Katsuhiko Mikoshiba
IRBIT [inositol 1,4,5-trisphosphate receptor (IP3R) binding protein released with inositol 1,4,5-trisphosphate (IP3)] is a multifunctional protein that regulates several target molecules such as ion channels, transporters, polyadenylation complex, and kinases. Through its interaction with multiple targets, IRBIT contributes to calcium signaling, electrolyte transport, mRNA processing, cell cycle, and neuronal function. However, the regulatory mechanism of IRBIT binding to particular targets is poorly understood...
April 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
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