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https://www.readbyqxmd.com/read/28108508/two-pore-channel-function-is-crucial-for-migration-of-invasive-cancer-cells
#1
Ong Nam Phuong Nguyen, Christian Grimm, Lina S Schneider, Yu-Kai Chao, Carina Atzberger, Karin Bartel, Anna Watermann, Melanie Ulrich, Doris Mayr, Christian Wahl-Schott, Martin Biel, Angelika M Vollmar
Metastatic invasion is the major cause of cancer-related deaths. In this study, we introduce two-pore channels (TPC), a recently described class of NAADP- and PI(3,5)P2-sensitive Ca2+-permeable cation channels in the endolysosomal system of cells, as candidate targets for the treatment of invasive cancers. Inhibition of the channel abrogated migration of metastatic cancer cells in vitro. Silencing or pharmacological inhibition of the two-pore channel TPC2 reduced lung metastasis of mammary mouse cancer cells...
January 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28107625/gold-nanoshell-mediated-remote-myotube-activation
#2
Attilio Marino, Satoshi Arai, Yanyan Hou, Andrea Degl'Innocenti, Valentina Cappello, Barbara Mazzolai, Young-Tae Chang, Virgilio Mattoli, Madoka Suzuki, Gianni Ciofani
Mild heat stimulation of muscle cells within the physiological range represents an intriguing approach for the modulation of their functions. In this work, photothermal conversion was exploited to remotely stimulate striated muscle cells by using gold nanoshells (NS) in combination with near-infrared (NIR) radiation. Temperature increments of approximately 5°C were recorded by using an intracellular fluorescent molecular thermometer and were demonstrated to efficiently induce myotube contraction. The mechanism at the base of this phenomenon was thoroughly investigated and was observed to be a Ca2+-independent event directly involving actin-myosin interactions...
January 20, 2017: ACS Nano
https://www.readbyqxmd.com/read/28107503/osteopontin-affects-insulin-vesicle-localization-and-ca2-homeostasis-in-pancreatic-beta-cells-from-female-mice
#3
Anna Wendt, Inês G Mollet, Anki Knutsson, Victor S Bolmgren, Anna Hultgårdh-Nilsson, Maria F Gomez, Lena Eliasson
Type 2 diabetic patients suffer from insulin resistance and reduced insulin secretion. Osteopontin (OPN), a versatile protein expressed in several tissues throughout the body including the islets of Langerhans, has previously been implicated in the development of insulin resistance. Here we have investigated the role of OPN in insulin secretion using an OPN knock out mouse model (OPN-/-). Ultra-structural analyzes of islets from OPN-/- and WT mice indicated weaker cell-cell connections between the islet cells in the OPN-/- mouse compared to WT...
2017: PloS One
https://www.readbyqxmd.com/read/28102080/n-oleoylglycine-induced-hyperphagia-was-associated-with-the-activation-of-agrp-neuron-by-cb1r
#4
Junguo Wu, Canjun Zhu, Liusong Yang, Zhonggang Wang, Lina Wang, Songbo Wang, Ping Gao, Yongliang Zhang, Qingyan Jiang, Gang Shu, Xiaotong Zhu
N-acyl amino acids (NAAAs) are conjugate products of fatty acids and amino acids, which are available in animal-derived food. We compared the effects of N-arachidonoyl glycine (NAGly), N-arachidonoyl serine (NASer), and N-Oleoylglycine (OLGly) on in vivo food intake and in vitro [Ca2+]i of AgRP neurons to identify the role of these compounds in energy homeostasis. The hypothalamic neuropeptide expression and anxiety behavior in response to OLGly were also tested. To further identify the underlying mechanism of OLGly on food intake, we first detected the expression level of potential OLGly receptors...
January 19, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28100666/t-type-ca2-channels-are-required-for-enhanced-sympathetic-axon-growth-by-tnf%C3%AE-reverse-signalling
#5
Lilian Kisiswa, Clara Erice, Laurent Ferron, Sean Wyatt, Catarina Osório, Annette C Dolphin, Alun M Davies
Tumour necrosis factor receptor 1 (TNFR1)-activated TNFα reverse signalling, in which membrane-integrated TNFα functions as a receptor for TNFR1, enhances axon growth from developing sympathetic neurons and plays a crucial role in establishing sympathetic innervation. Here, we have investigated the link between TNFα reverse signalling and axon growth in cultured sympathetic neurons. TNFR1-activated TNFα reverse signalling promotes Ca(2+) influx, and highly selective T-type Ca(2+) channel inhibitors, but not pharmacological inhibitors of L-type, N-type and P/Q-type Ca(2+) channels, prevented enhanced axon growth...
January 2017: Open Biology
https://www.readbyqxmd.com/read/28100643/fluid-shear-stress-increases-transepithelial-transport-of-ca2-in-ciliated-distal-convoluted-and-connecting-tubule-cells
#6
Sami G Mohammed, Francisco J Arjona, Femke Latta, René J M Bindels, Ronald Roepman, Joost G J Hoenderop
In kidney, transcellular transport of Ca(2+) is mediated by transient receptor potential vanilloid 5 and Na(+)-Ca(2+) exchanger 1 proteins in distal convoluted and connecting tubules (DCT and CNT, respectively). It is not yet understood how DCT/CNT cells can adapt to differences in tubular flow rate and, consequently, Ca(2+) load. This study aims to elucidate the molecular mechanisms by which DCT/CNT cells sense fluid dynamics to control transepithelial Ca(2+) reabsorption and whether their primary cilia play an active role in this process...
January 18, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28100639/munc13-4-functions-as-a-ca2-sensor-for-homotypic-secretory-granule-fusion-to-generate-endosomal-exocytic-vacuoles
#7
Sang Su Woo, Declan J James, Thomas F J Martin
Munc13-4 is a Ca(2+)-dependent SNARE- and phospholipid-binding protein that localizes to and primes secretory granules (SGs) for Ca(2+)-evoked secretion in various secretory cells. Studies in mast cell-like RBL-2H3 cells provides direct evidence that Munc13-4 with its two Ca(2+)-binding C2 domains functions as a Ca(2+) sensor for SG exocytosis. Unexpectedly, Ca(2+) stimulation also generated large (>2.4 μm diameter) Munc13-4(+)/Rab7(+)/Rab11(+) endosomal vacuoles. Vacuole generation involved the homotypic fusion of Munc13-4(+)/Rab7(+) SGs followed by a merge with Rab11(+) endosomes, and depended on Ca(2+) binding to Munc13-4...
January 18, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28098450/the-serum-amyloid-p-component-sap-interactome-in-human-plasma-containing-physiological-calcium-levels
#8
Ebbe Toftgaard Poulsen, Kata Wolff Pedersen, Anna Maria Marzeda, Jan Johannes Enghild
The pentraxin serum amyloid p component (SAP) is secreted by the liver and found in plasma at a concentration of approximately 30 mg/L. SAP is a 25 kDa homo-pentamer known to bind both protein and non-protein ligands, all in a calcium-dependent manner. The function of SAP is unclear, but likely involves the humoral innate immune system spanning the complement system, inflammation, and coagulation. Also, SAP is known to binding to the generic structure of amyloid deposits and possibly to protect these against proteolysis...
January 18, 2017: Biochemistry
https://www.readbyqxmd.com/read/28097171/structural-insights-into-the-effects-of-charge-reversal-substitutions-at-the-surface-of-horseradish-peroxidase
#9
Leila Navapour, Navid Mogharrab
Horseradish peroxidase (HRP), has gained significant interests in biotechnology, especially in biosensor field and diagnostic test kits. Hence, its solvent-exposed lysine residues 174, 232, and 241 have been frequently modified with the aim of improving its stability and catalytic efficiency. In this computational study, we investigated the effects of Lys-to-Glu substitutions on HRP structure to model charge-reversal manipulations at the enzyme surface. Simulation results implied that upon these substitutions, the number of stable hydrogen bonds and α-helical content of HRP are increased and the proximal Ca2+ binding pocket becomes more integrated...
September 2016: Molecular Biology Research Communications
https://www.readbyqxmd.com/read/28096465/sequences-within-the-c-terminus-of-the-metabotropic-glutamate-receptor-mglur5-are-responsible-for-inner-nuclear-membrane-localization
#10
Ismail Sergin, Yuh-Jiin I Jong, Steven K Harmon, Vikas Kumar, Karen L O'Malley
Traditionally G-protein coupled receptors (GPCR) are thought to be located on the cell surface where they transmit extracellular signals to the cytoplasm. However recent studies indicate that some GPCRs are also localized to various subcellular compartments such as the nucleus where they appear required for various biological functions. For example, the metabotropic glutamate receptor 5, mGluR5, is concentrated at the inner nuclear membrane (INM) where it mediates Ca2+ changes in the nucleoplasm by coupling with Gq/11...
January 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28096464/functional-transformation-of-c-reactive-protein-by-hydrogen-peroxide
#11
Sanjay K Singh, Avinash Thirumalai, Asmita Pathak, Donald N Ngwa, Alok Agrawal
C-reactive protein (CRP) is present at sites of inflammation including amyloid plaques, atherosclerotic lesions and arthritic joints. CRP, in its native pentameric structural conformation, binds to cells and molecules which have exposed phosphocholine (PCh) groups. CRP, in its non-native pentameric structural conformation, binds to a variety of deposited, denatured and aggregated proteins, in addition to binding to PCh-containing substances. In this study, we investigated the effects of hydrogen peroxide (H2O2), a prototypical reactive oxygen species and which is also present at sites of inflammation, on the ligand recognition function of CRP...
January 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28096168/sk-channel-enhancers-attenuate-ca2-dependent-arrhythmia-in-hypertrophic-hearts-by-regulating-mito-ros-dependent-oxidation-and-activity-of-ryr
#12
Tae Yun Kim, Radmila Terentyeva, Karim H F Roder, Weiyan Li, Man Liu, Ian Greener, Shanna Hamilton, Iuliia Polina, Kevin R Murphy, Richard T Clements, Samuel C Dudley, Gideon Koren, Bum-Rak Choi, Dmitry Terentyev
AIM: s: Plasmamembrane small conductance Ca<su2+p>-activated K<su+ p > (SK) channels were implicated in ventricular arrhythmias in infarcted and failing hearts. Recently, SK channels were detected in the mitochondria inner membrane (mSK), and their activation protected from acute ischemia-reperfusion injury by reducing intracellular levels of reactive oxygen species (ROS). We hypothesized that mSK play an important role in regulating mitochondrial function in chronic cardiac diseases...
January 17, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28087991/an-exceptionally-selective-dna-cooperatively-binding-two-ca2-ions
#13
Wenhu Zhou, Runjhun Saran, Po-Jung Jimmy Huang, Jinsong Ding, Juewen Liu
Ca2+ is a highly important metal ion in biology and in the environment, leading to extensive work in developing sensors for Ca2+ detection. While many Ca2+ binding proteins are known, few nucleic acids can selectively bind Ca2+. DNA-based biosensors are attractive for its high stability and excellent programmability. Herein, we report a RNA-cleaving DNAzyme named EtNa cooperatively binding two Ca2+ ions but only one Mg2+. Four DNAzymes with known Ca2+-dependent activity were compared, and the EtNa has the best selectivity...
January 14, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28087698/inhibition-of-trpml1-by-lysosomal-adenosine-involved-in-severe-combined-immunodeficiency-diseases
#14
Xi Zoë Zhong, Yuanjie Zou, Xue Sun, Gaofeng Dong, Qi Cao, Aditya Pandey, Jan K Rainey, Xiaojuan Zhu, Xian-Ping Dong
Impaired adenosine homeostasis has been associated with numerous human diseases. Lysosomes are referred to as the cellular recycling centers which generate adenosine by breaking down nucleic acids or ATP. Recent studies have suggested that lysosomal adenosine overload causes lysosome defects which phenocopy patients with mutations in TRPML1, a lysosomal Ca2+ channel, suggesting that lysosomal adenosine overload may impair TRPML1 and then lead to subsequent lysosomal dysfunction. In this study, we demonstrate that lysosomal adenosine is elevated by deleting adenosine deaminase (ADA), an enzyme responsible for adenosine degradation...
January 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28087621/the-hook-region-of-voltage-gated-ca2-channel-%C3%AE-subunits-senses-and-transmits-pip2-signals-to-the-gate
#15
Cheon-Gyu Park, Yongsoo Park, Byung-Chang Suh
The β subunit of voltage-gated Ca(2+) (CaV) channels plays an important role in regulating gating of the α1 pore-forming subunit and its regulation by phosphatidylinositol 4,5-bisphosphate (PIP2). Subcellular localization of the CaV β subunit is critical for this effect; N-terminal-dependent membrane targeting of the β subunit slows inactivation and decreases PIP2 sensitivity. Here, we provide evidence that the HOOK region of the β subunit plays an important role in the regulation of CaV biophysics. Based on amino acid composition, we broadly divide the HOOK region into three domains: S (polyserine), A (polyacidic), and B (polybasic)...
January 13, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28087597/membrane-depolarizing-channel-blockers-induce-selective-glioma-cell-death-by-impairing-nutrient-transport-and-unfolded-protein-amino-acid-responses
#16
Mia Niklasson, Gianluca Maddalo, Zuzana Sramkova, Ercan Mutlu, Shimei Wee, Petra Sekyrova, Linnéa Schmidt, Nicolas Fritz, Ivar Dehnisch, Gregorios Kyriatzis, Michaela Krafcikova, Brittany B Carson, Jennifer Feenstra, Voichita D Marinescu, Anna Segerman, Martin Haraldsson, Anna-Lena Gustavsson, Lars Gj Hammarström, Annika Jenmalm-Jensen, Lene Uhrbom, A F Maarten Altelaar, Sten Linnarsson, Per Uhlén, Lukas Trantirek, C Theresa Vincent, Sven Nelander, Per Øyvind Enger, Michael Andäng
Glioma-initiating cells (GIC) are considered the underlying cause of recurrences of aggressive glioblastomas, replenishing the tumor population and undermining the efficacy of conventional chemotherapy. Here we report the discovery that inhibiting T-type voltage-gated Ca2+ and KCa channels can effectively induce selective cell death of GIC and increase host survival in an orthotopic mouse model of human glioma. At present, the precise cellular pathways affected by the drugs affecting these channels are unknown...
January 13, 2017: Cancer Research
https://www.readbyqxmd.com/read/28077617/calcineurin-the-ca2-dependent-phosphatase-regulates-rga2-a-cdc42-gtpase-activating-protein-to-modulate-pheromone-signaling
#17
Nina Ly, Martha S Cyert
Calcineurin, the conserved Ca(2+)/calmodulin-activated phosphatase, is required for viability during prolonged exposure to pheromone, and acts through multiple substrates to down regulate yeast pheromone signaling. Calcineurin regulates Dig2 and Rod1/Art4 to inhibit mating-induced gene expression and activate receptor internalization, respectively. Recent systematic approaches identified Rga2, a GTPase activating protein (GAP) for the Cdc42 Rho-type GTPase, as a calcineurin substrate. Here, we establish a physiological context for this regulation, and show that calcineurin dephosphorylates and positively regulates Rga2 during pheromone signaling...
January 11, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28077437/sensitized-signalling-between-l-type-ca2-channels-and-ryanodine-receptors-in-the-absence-or-inhibition-of-fkbp12-6-in-cardiomyocytes
#18
Yan-Ting Zhao, Yun-Bo Guo, Lei Gu, Xue-Xin Fan, Hua-Qian Yang, Zheng Chen, Peng Zhou, Qi Yuan, Guang-Ju Ji, Shi-Qiang Wang
AIMS: The heart contraction is controlled by the Ca(2+)-induced Ca(2+ )release (CICR) between L-type Ca(2+ )channels and ryanodine receptors (RyRs). The FK506-binding protein FKBP12.6 binds to RyR subunits, but its role in stabilizing RyR function has been debated for long. Recent reports of high-resolution RyR structure show that the HD2 domain that binds to the SPRY2 domain of neighbouring subunit in FKBP-bound RyR1 is detached and invisible in FKBP-null RyR2. The present study was to test the consequence of FKBP12...
January 10, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28074656/atomistic-modeling-of-ion-conduction-through-the-voltage-sensing-domain-of-the-shaker-k-ion-channel
#19
Mona L Wood, J Alfredo Freites, Francesco Tombola, Douglas J Tobias
Voltage-sensing domains (VSDs) are modular membrane protein units that sense changes in the membrane electrostatic potential, and through conformational changes, regulate a specific function. The VSDs of voltage-dependent K+, Na+, and Ca2+ channels do not conduct ions under physiological conditions, but they can become ion-permeable under pathological conditions through mutations in the voltage sensor, particularly of basic residues (mostly arginines) in the S4 helix. Relatively little is known about the underlying mechanisms of conduction through VSDs...
January 11, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28072824/d19s-mutation-of-the-cationic-cysteine-rich-protein-paf-novel-insights-into-its-structural-dynamics-thermal-unfolding-and-antifungal-function
#20
Christoph Sonderegger, Ádám Fizil, Laura Burtscher, Dorottya Hajdu, Alberto Muñoz, Zoltán Gáspári, Nick D Read, Gyula Batta, Florentine Marx
The cysteine-rich, cationic, antifungal protein PAF is abundantly secreted into the culture supernatant of the filamentous Ascomycete Penicillium chrysogenum. The five β-strands of PAF form a compact β-barrel that is stabilized by three disulphide bonds. The folding of PAF allows the formation of four surface-exposed loops and distinct charged motifs on the protein surface that might regulate the interaction of PAF with the sensitive target fungus. The growth inhibitory activity of this highly stable protein against opportunistic fungal pathogens provides great potential in antifungal drug research...
2017: PloS One
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