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Calcium Sensor Receptor

Bernhard Stenger, Tanja Popp, Harald John, Markus Siegert, Amelie Tsoutsoulopoulos, Annette Schmidt, Harald Mückter, Thomas Gudermann, Horst Thiermann, Dirk Steinritz
Transient receptor potential family channels (TRPs) have been identified as relevant targets in many pharmacological as well as toxicological studies. TRP channels are ubiquitously expressed in different tissues and act among others as sensors for different external stimuli, such as mechanical stress or noxious impacts. Recent studies suggest that one member of this family, the transient receptor potential ankyrin 1 cation channel (TRPA1), is involved in pain, itch, and various diseases, suggesting TRPA1 as a potential therapeutic target...
October 13, 2016: Archives of Toxicology
Birol Cabukusta, Jan A Köhlen, Christian P Richter, Changjiang You, Joost C M Holthuis
Single-molecule photobleaching has emerged as a powerful non-invasive approach to extract the stoichiometry of multimeric membrane proteins in their native cellular environment. However, this method has mainly been used to determine the subunit composition of ion channels and receptors at the plasma membrane. In here we applied single-molecule photobleaching to analyse the oligomeric state of an ER-resident candidate ceramide sensor protein, SMSr/SAMD8. Co-immunoprecipitation and chemical crosslinking studies previously revealed that the N-terminal sterile alpha motif or SAM domain of SMSr drives self-assembly of the protein into oligomers and that SMSr oligomerization is promoted by curcumin, a drug known to perturb ER ceramide and calcium homeostasis...
October 10, 2016: Journal of Biological Chemistry
Deepika Sharma, Brijendra Kumar Tiwari, Subhash Mehto, Cecil Antony, Gunjan Kak, Yogendra Singh, Krishnamurthy Natarajan
The prevalence of Mycobacterium tuberculosis (M. tb) strains eliciting drug resistance has necessitated the need for understanding the complexities of host pathogen interactions. The regulation of calcium homeostasis by Voltage Gated Calcium Channel (VGCCs) upon M. tb infection has recently assumed importance in this area. We previously showed a suppressor role of VGCC during M. tb infections and recently reported the mechanisms of its regulation by M. tb. Here in this report, we further characterize the role of VGCC in mediating defence responses of macrophages during mycobacterial infection...
2016: PloS One
Hsiang-Han Su, Hsin-Ting Lin, Jau-Ling Suen, Chau Chyun Sheu, Kazunari K Yokoyama, Shau-Ku Huang, Chih Mei Cheng
Pulmonary fibroblast migration and differentiation are critical events in fibrogenesis; meanwhile, fibrosis characterizes the pathology of many respiratory diseases. The role of aryl hydrocarbon receptor (AhR), a unique cellular chemical sensor, has been suggested in tissue fibrosis, but the mechanisms through which the AhR-ligand axis influences the fibrotic process remain undefined. In this study, the potential impact of the AhR-ligand axis on pulmonary fibroblast migration and differentiation was analyzed using human primary lung fibroblasts HFL-1 and CCL-202 cells...
September 30, 2016: Toxicology
Amédée des Georges, Oliver B Clarke, Ran Zalk, Qi Yuan, Kendall J Condon, Robert A Grassucci, Wayne A Hendrickson, Andrew R Marks, Joachim Frank
The type-1 ryanodine receptor (RyR1) is an intracellular calcium (Ca(2+)) release channel required for skeletal muscle contraction. Here, we present cryo-EM reconstructions of RyR1 in multiple functional states revealing the structural basis of channel gating and ligand-dependent activation. Binding sites for the channel activators Ca(2+), ATP, and caffeine were identified at interdomain interfaces of the C-terminal domain. Either ATP or Ca(2+) alone induces conformational changes in the cytoplasmic assembly ("priming"), without pore dilation...
September 22, 2016: Cell
Judith A Stolwijk, Xuexin Zhang, Maxime Gueguinou, Wei Zhang, Khalid Matrougui, Christian Renken, Mohamed Trebak
Endothelial barrier function is tightly regulated by plasma membrane receptors and is crucial for tissue fluid homeostasis; its dysfunction causes disease, including sepsis and inflammation. The ubiquitous activation of Ca2+ signaling upon phospholipase C (PLC)-coupled receptor ligation leads quite naturally to the assumption that Ca2+ signaling is required for receptor-regulated endothelial barrier function. This widespread hypothesis draws analogy from smooth muscle and proposes the requirement of G protein coupled receptor (GPCR)-generated Ca2+ signaling in activating the endothelial contractile apparatus and generating inter-endothelial gaps...
September 13, 2016: Journal of Biological Chemistry
Xueyan Peng, Meagan Moore, Aditi Mathur, Yang Zhou, Huanxing Sun, Ye Gan, Jose D Herazo-Maya, Naftali Kaminski, Xinyuan Hu, Hongyi Pan, Changwan Ryu, Awo Osafo-Addo, Robert J Homer, Carol Feghali-Bostwick, Wassim Fares, Mridu Gulati, Buqu Hu, Chun-Geun Lee, Jack A Elias, Erica L Herzog
Pulmonary fibrosis is a progressive and often fatal condition that is believed to be partially orchestrated by macrophages. Mechanisms that control migration of these cells into and within the lung remain undefined. We evaluated the contributions of the semaphorin receptor, plexin C1 (PLXNC1), and the exocytic calcium sensor, synaptotagmin 7 (Syt7), in these processes. We evaluated the role of PLXNC1 in macrophage migration by using Boyden chambers and scratch tests, characterized its contribution to experimentally induced lung fibrosis in mice, and defined the mechanism for our observations...
September 8, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Christopher E Woods, Ching Shang, Fouad Taghavi, Peter Downey, Adrian Zalewski, Gabriel R Rubio, Jing Liu, Julian R Homburger, Zachary Grunwald, Wei Qi, Christian Bollensdorff, Porama Thanaporn, Ayyaz Ali, R Kirk Riemer, Peter Kohl, Daria Mochly-Rosen, Edward Gerstenfeld, Stephen Large, Ziad A Ali, Euan A Ashley
BACKGROUND: Survival after sudden cardiac arrest is limited by postarrest myocardial dysfunction, but understanding of this phenomenon is constrained by a lack of data from a physiological model of disease. In this study, we established an in vivo model of cardiac arrest and resuscitation, characterized the biology of the associated myocardial dysfunction, and tested novel therapeutic strategies. METHODS: We developed rodent models of in vivo postarrest myocardial dysfunction using extracorporeal membrane oxygenation resuscitation followed by invasive hemodynamics measurement...
September 27, 2016: Circulation
Xuhua Mao, Jianfeng Zhang, Yue Han, Chao Luan, Yu Hu, Zhimin Hao, Min Chen
Antigen specific B cells undergo a process termed affinity maturation in the germinal centers of secondary lymphoid organs where B cells with high affinity receptors are selected to mature into antibody-producing cells or to the memory B cell pool. It is known that B cell antigen receptor (BCR) signaling plays pivotal role in this selection process. Calcium influx is an essential component of BCR signaling. The current report is to determine the effect of calcium influx on antibody affinity maturation. In our studies, mice deficient for both endoplasmic reticulum calciumsensor Stim1 and Stim2 was immunized with T-cell dependent and independent antigens...
August 27, 2016: Oncotarget
Jessica A Fawley, Mackenzie E Hofmann, Michael C Andresen
UNLABELLED: Most craniosensory afferents have unmyelinated axons expressing TRP Vanilloid 1 (TRPV1) receptors in synaptic terminals at the solitary tract nucleus (NTS). Neurotransmission from these synapses is characterized by substantial asynchronous EPSCs following action potential-synched EPSCs and high spontaneous rates that are thermally sensitive. The present studies blocked voltage-activated calcium channels (CaV) using the nonselective CaV blocker Cd(2+) or the specific N-type blocker ω-conotoxin GVIA to examine the calcium dependence of the synchronous, asynchronous, spontaneous, and thermally gated modes of release...
August 24, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Yi Sul Cho, Chang Hyun Ryu, Jong Hwa Won, Hue Vang, Seog Bae Oh, Jin Young Ro, Yong Chul Bae
Accumulating evidence indicates that odontoblasts act as sensor cells, capable of triggering action potentials in adjacent pulpal nociceptive axons, suggesting a paracrine signaling via a currently unknown mediator. Since glutamate can mediate signaling by non-neuronal cells, and peripheral axons may express glutamate receptors (GluR), we hypothesized that the expression of high levels of glutamate, and of sensory receptors in odontoblasts, combined with an expression of GluR in adjacent pulpal axons, is the morphological basis for odontoblastic sensory signaling...
October 29, 2016: Neuroscience
Jaekyun Choi, Lena van Giesen, Min Sung Choi, KyeongJin Kang, Simon G Sprecher, Jae Young Kwon
The sense of taste is an essential chemosensory modality that enables animals to identify appropriate food sources and control feeding behavior. In particular, the recognition of bitter taste prevents animals from feeding on harmful substances. Feeding is a complex behavior comprised of multiple steps, and food quality is continuously assessed. We here examined the role of pharyngeal gustatory organs in ingestion behavior. As a first step, we constructed a gustatory receptor-to-neuron map of the larval pharyngeal sense organs, and examined corresponding gustatory receptor neuron (GRN) projections in the larval brain...
2016: Frontiers in Cellular Neuroscience
Lieqi Tang, Catherine Y Cheng, Xiangrong Sun, Alexandra J Pedicone, Mansour Mohamadzadeh, Sam X Cheng
Different from other epithelia, the intestinal epithelium has the complex task of providing a barrier impeding the entry of toxins, food antigens, and microbes, while at the same time allowing for the transfer of nutrients, electrolytes, water, and microbial metabolites. These molecules/organisms are transported either transcellularly, crossing the apical and basolateral membranes of enterocytes, or paracellularly, passing through the space between enterocytes. Accordingly, the intestinal epithelium can affect energy metabolism, fluid balance, as well as immune response and tolerance...
2016: Frontiers in Physiology
Ramona Pais, Juraj Rievaj, Pierre Larraufie, Fiona Gribble, Frank Reimann
Angiotensin II (Ang II) is the key hormone mediator of the renin angiotensin system, which regulates blood pressure and fluid and electrolyte balance in the body. Here we report that in the colonic epithelium, the Ang II type 1 receptor is highly and exclusively expressed in enteroendocrine L cells, which produce the gut hormones glucagon-like peptide-1 and peptide YY (PYY). Ang II stimulated glucagon-like peptide-1 and PYY release from primary cultures of mouse and human colon, which was antagonized by the specific Ang II type 1 receptor blocker candesartan...
October 2016: Endocrinology
Ying Lai, Ucheor B Choi, Yunxiang Zhang, Minglei Zhao, Richard A Pfuetzner, Austin L Wang, Jiajie Diao, Axel T Brunger
Complexin activates Ca(2+)-triggered neurotransmitter release and regulates spontaneous release in the presynaptic terminal by cooperating with the neuronal soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) and the Ca(2+)-sensor synaptotagmin. The N-terminal domain of complexin is important for activation, but its molecular mechanism is still poorly understood. Here, we observed that a split pair of N-terminal and central domain fragments of complexin is sufficient to activate Ca(2+)-triggered release using a reconstituted single-vesicle fusion assay, suggesting that the N-terminal domain acts as an independent module within the synaptic fusion machinery...
August 9, 2016: Proceedings of the National Academy of Sciences of the United States of America
S Beceiro, J N Radin, R Chatuvedi, M B Piazuelo, D J Horvarth, H Cortado, Y Gu, B Dixon, C Gu, I Lange, D-Lt Koomoa, K T Wilson, H M S Algood, S Partida-Sánchez
Calcium signaling in phagocytes is essential for cellular activation, migration, and the potential resolution of infection or inflammation. The generation of reactive oxygen species (ROS) via activation of NADPH (nicotinamide adenine dinucleotide phosphate)-oxidase activity in macrophages has been linked to altered intracellular calcium concentrations. Because of its role as an oxidative stress sensor in phagocytes, we investigated the function of the cation channel transient receptor potential melastatin 2 (TRPM2) in macrophages during oxidative stress responses induced by Helicobacter pylori infection...
July 20, 2016: Mucosal Immunology
Jakobus van Unen, Ali Rashidfarrokhi, Eelco Hoogendoorn, Marten Postma, Theodorus W J Gadella, Joachim Goedhart
Genetically encoded biosensors based on Förster resonance energy transfer (FRET) can visualize responses of individual cells in real time. Here, we evaluated whether FRET-based biosensors provide sufficient contrast and specificity to measure activity of G-protein-coupled receptors. The four histamine receptor subtypes (H1R, H2R, H3R, and H4R) respond to the ligand histamine by activating three canonical heterotrimeric G-protein-mediated signaling pathways with a reported high degree of specificity. Using FRET-based biosensors, we demonstrate that H1R activates Gαq...
September 2016: Molecular Pharmacology
Anna Hynkova, Lenka Marsakova, Jana Vaskova, Viktorie Vlachova
Human transient receptor potential ankyrin channel 1 (TRPA1) is a polymodal sensor implicated in pain, inflammation and itching. An important locus for TRPA1 regulation is the cytoplasmic N-terminal domain, through which various exogenous electrophilic compounds such as allyl-isothiocyanate from mustard oil or cinnamaldehyde from cinnamon activate primary afferent nociceptors. This major region is comprised of a tandem set of 17 ankyrin repeats (AR1-AR17), five of them contain a strictly conserved T/SPLH tetrapeptide motif, a hallmark of an important and evolutionarily conserved contribution to conformational stability...
2016: Scientific Reports
Grant R J Gordon, Clare Howarth, Brian A MacVicar
Altering cerebral blood flow through the control of cerebral vessel diameter is critical so that the delivery of molecules important for proper brain functioning is matched to the activity level of neurons. Although the close relationship of brain glia known as astrocytes with cerebral blood vessels has long been recognized, it is only recently that these cells have been demonstrated to translate information on the activity level and energy demands of neurons to the vasculature. In particular, astrocytes respond to elevations in extracellular glutamate as a consequence of synaptic transmission through the activation of group 1 metabotropic glutamate receptors...
2016: Advances in Experimental Medicine and Biology
Eugene A Permyakov, Vladimir N Uversky, Sergei E Permyakov
Cytokine interleukin-11 (IL-11) is a multifunctional protein with diverse roles in the normal cell signaling and in various pathologies. The structure of IL-11 is characterized by a four-helix bundle motif comprising two pairs of antiparallel α-helices arranged in an up-up-down-down configuration. Evaluation of the intrinsic disorder predisposition of human IL-11 by several computational tools clearly shows that this protein is predicted to have functional disordered regions potentially involved in interaction with natural binding partners...
September 2016: Cell Biochemistry and Biophysics
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