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Adenylyl cyclases

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https://www.readbyqxmd.com/read/29229700/flexible-hinges-in-bacterial-chemoreceptors
#1
Narahari Akkaladevi, Filiz Bunyak, David Stalla, Tommi A White, Gerald L Hazelbauer
Transmembrane bacterial chemoreceptors are extended, rod-shaped homodimers with ligand-binding sites at one end and interaction sites for formation of signaling complexes and histidine kinase control at the other. There are atomic-resolution structures of chemoreceptor fragments but not of intact, membrane-inserted receptors. Electron tomography of in vivo signaling complex arrays lack distinct densities for chemoreceptor rods away from the well-ordered base plate region, implying structural heterogeneity. We investigated using negative staining, transmission electron microscopy and image analysis to characterize molecular shapes of intact homodimers of Escherichia coli aspartate receptor Tar rendered functional by insertion into Nanodisc-provided E...
December 11, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/29229010/relative-importance-of-phosphatidylinositol-3-kinase-pi3k-akt-and-mitogen-activated-protein-kinase-mapk3-1-signaling-during-maturational-steroid-induced-meiotic-g2-m1-transition-in-zebrafish-oocytes
#2
Debabrata Das, Poulomi Nath, Soumojit Pal, Sudip Hajra, Pritha Ghosh, Sudipta Maitra
Participation and relative importance of phosphatidylinositol-3 kinase (PI3K) and mitogen-activated protein kinase (MAPK) signalling, either alone or in combination, have been investigated during 17α,20β-dihydroxy-4-pregnen-3-one (DHP)-induced meiotic G2-M1 transition in denuded zebrafish oocyte. Results demonstrate that concomitant with rapid phosphorylation (activation) of Akt (Ser473) and MAPK (ERK1/2) at as early as 15 min of incubation, DHP stimulation promotes enhanced an GVBD response and histone H1 kinase activation between 1 and 5 h in full-grown oocytes in vitro...
December 12, 2017: Zygote: the Biology of Gametes and Early Embryos
https://www.readbyqxmd.com/read/29222746/cadmium-favors-f-actin-depolymerization-in-rat-renal-mesangial-cells-by-site-specific-disulfide-based-dimerization-of-the-cap1-protein
#3
Ying Liu, Weiqun Xiao, Manasi Shinde, Jeffrey Field, Douglas M Templeton
Cadmium is a toxic metal that produces oxidative stress and has been shown to disrupt the actin cytoskeleton in rat renal mesangial cells (RMC). In a survey of proteins that might undergo Cd2+-dependent disulfide crosslinking, we identified the adenylyl cyclase-associated protein, CAP1, as undergoing a dimerization in response to Cd2+ (5-40 µM) that was sensitive to disulfide reducing agents, was reproduced by the disulfide crosslinking agent diamide, and was shown by site-directed mutagenesis to involve the Cys29 residue of the protein...
December 8, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/29217670/camp-signaling-compartmentation-adenylyl-cyclases-as-anchors-of-dynamic-signaling-complexes
#4
Timothy B Johnstone, Shailesh R Agarwal, Robert D Harvey, Rennolds S Ostrom
It is widely accepted that cAMP signaling is compartmentalized within cells. However, our knowledge of how receptors, cAMP signaling enzymes, effectors and other key proteins form specific signaling complexes to regulate specific cell responses is limited. The multi-component nature of these systems and the spatiotemporal dynamics involved as proteins interact and move within a cell, make cAMP responses highly complex. Adenylyl cyclases, the enzymatic source of cAMP production, are key starting points for understanding cAMP compartments and defining the functional signaling complexes...
December 7, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/29212811/altered-expression-of-hepatic-%C3%AE-adrenergic-receptors-in-aging-rats-implications-for-age-related-metabolic-dysfunction-in-liver
#5
Yun Shi, Zhen-Ju Shu, Hanzhou Wang, Jeffrey L Barnes, Chih-Ko Yeh, Paramita M Ghosh, Michael S Katz, Amrita Kamat
Increased β-adrenergic receptor (β-AR)-mediated activation of adenylyl cyclase (AC) in rat liver during aging has been linked to age-related increases in hepatic glucose output and hepatosteatosis. In this study we investigated the expression of β-ARs, individual receptor subtypes, and G protein-coupled receptor (GPCR) regulatory proteins in livers from aging rats. Radioligand binding studies demonstrated that β-AR density increased by >3-fold in hepatocyte membranes from senescent (24 mo old) compared to young adult (7 mo old) rats, and that this phenomenon was blocked by food restriction which is known to retard aging processes in rodents...
December 6, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29203545/bordetella-pertussis-adenylate-cyclase-toxin-disrupts-functional-integrity-of-bronchial-epithelial-layers
#6
Shakir Hasan, Nikhil Nitin Kulkarni, Arni Asbjarnarson, Irena Linhartova, Radim Osicka, Peter Sebo, Gudmundur H Gudmundsson
Airway epithelium restricts penetration of inhaled pathogens into the underlying tissue and plays a crucial role in innate immune defense against respiratory infections. The whooping cough agent, Bordetella pertussis, adheres to ciliated cells of human airway epithelium and subverts its defense functions through the action of secreted toxins and other virulence factors. We have examined the impact of B. pertussis infection and of adenylate cyclase toxin (CyaA) action on the functional integrity of air-liquid interface (ALI)-cultured human bronchial epithelial cells...
December 4, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/29192658/selective-adenylyl-cyclase-type-1-inhibitors-as-potential-opioid-alternatives-for-chronic-pain
#7
Val J Watts
No abstract text is available yet for this article.
January 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29183785/ablation-of-gs%C3%AE-signaling-in-osteoclast-progenitor-cells-adversely-affects-skeletal-bone-maintenance
#8
REVIEW
Girish Ramaswamy, John Fong, Niambi Brewer, Hyunsoo Kim, Deyu Zhang, Yongwon Choi, Frederick S Kaplan, Eileen M Shore
Gsα, the alpha stimulatory subunit of heterotrimeric G proteins that activates downstream signaling through the adenylyl cyclase and cAMP/PKA pathway, plays an important role in bone development and remodeling. The role of Gsα in mesenchymal stem cell (MSC) differentiation to osteoblasts has been demonstrated in several mouse models of Gsα inactivation. Previously, using mice with heterozygous germline deletion of Gsα (Gnas+/p-), we identified a novel additional role for Gsα in bone remodeling, and showed the importance of Gnas in maintaining bone quality by regulating osteoclast differentiation and function...
November 25, 2017: Bone
https://www.readbyqxmd.com/read/29176673/phosphoproteomics-of-camp-signaling-of-bordetella-adenylate-cyclase-toxin-in-mouse-dendritic-cells
#9
Jakub Novák, Ivo Fabrik, Irena Linhartová, Marek Link, Ondřej Černý, Jiří Stulík, Peter Šebo
The adenylate cyclase toxin (CyaA) of the whooping cough agent Bordetella pertussis subverts immune functions of host myeloid cells expressing the αMβ2 integrin (CD11b/CD18, CR3 or Mac-1). CyaA delivers into cytosol of cells an extremely catalytically active adenylyl cyclase enzyme, which disrupts the innate and adaptive immune functions of phagocytes through unregulated production of the key signaling molecule cAMP. We have used phosphoproteomics to analyze cAMP signaling of CyaA in murine bone marrow-derived dendritic cells...
November 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29175000/cyclic-nucleotide-signaling-changes-associated-with-normal-aging-and-age-related-diseases-of-the-brain
#10
REVIEW
Michy P Kelly
Deficits in brain function that are associated with aging and age-related diseases benefit very little from currently available therapies, suggesting a better understanding of the underlying molecular mechanisms is needed to develop improved drugs. Here, we review the literature to test the hypothesis that a break down in cyclic nucleotide signaling at the level of synthesis, execution, and/or degradation may contribute to these deficits. A number of findings have been reported in both the human and animal model literature that point to brain region-specific changes in Galphas (a...
November 23, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29161035/synthesis-of-photoswitchable-%C3%AE-9-tetrahydrocannabinol-derivatives-enables-optical-control-of-cannabinoid-receptor-1-signaling
#11
Matthias Westphal, Michael Andreas Schafroth, Roman Sarott, Michael Imhof, Christian Bold, Philipp Leippe, Amey Dhopeshwarkar, Jessica Grandner, Vsevolod Katritch, Ken Mackie, Dirk Trauner, Erick M Carreira, James Allen Frank
The cannabinoid receptor 1 (CB1) is an inhibitory G protein-coupled receptor abundantly expressed in the central nerv-ous system. It has rich pharmacology and largely accounts for the recreational use of cannabis. We describe efficient asymmetric syntheses of four photoswitchable Δ(9)-tetrahydrocannabinol derivatives (azo-THCs) from a central building block 3-Br-THC. Using electrophysiology and a FRET-based cAMP assay, two compounds are identified as potent CB1 agonists that change their effect upon illumination...
November 21, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29159836/mechanisms-of-calcium-sequestration-by-isolated-malpighian-tubules-of-the-house-cricket-acheta-domesticus
#12
Austin Browne, Michael J O'Donnell
Hemolymph calcium homeostasis in insects is achieved by the Malpighian tubules, primarily by sequestering excess Ca(2+) within internal calcium stores (Ca-rich granules) most often located within type I (principal) tubule cells. Using both the scanning ion-selective electrode technique and the Ramsay secretion assay this study provides the first measurements of basolateral and transepithelial Ca(2+) fluxes across the Malpighian tubules of an Orthopteran insect, the house cricket Acheta domesticus. Ca(2+) transport was specific to midtubule segments, where 97% of the Ca(2+) entering the tubule is sequestered within intracellular calcium stores and the remaining 3% is secreted into the lumen...
November 21, 2017: Archives of Insect Biochemistry and Physiology
https://www.readbyqxmd.com/read/29158149/the-role-of-hydrogen-sulfide-in-cyclic-nucleotide-signaling
#13
REVIEW
Xu Cao, Zhiyuan Wu, Siping Xiong, Lei Cao, Gautam Sethi, Jin-Song Bian
Hydrogen sulfide (H2S) is recognized as an endogenous gaseous transmitter alongside nitric oxide (NO) and carbon monoxide (CO). By integrating into multiple signaling pathways, H2S elicits biological functions in various mammalian systems. Among these pathways, cyclic nucleotide signaling has gradually gained attention in the past decade. Based on current evidence, it seems that H2S may differentially affect the activity of resting adenylyl cyclases (ACs) and activated ACs, therefore playing a dual role in the regulation of cyclic adenosine monophosphate (cAMP) mediated signaling...
November 17, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29141923/src-family-kinase-inhibitors-blunt-the-pacap-induced-pac1-receptor-endocytosis-phosphorylation-of-erk-and-increase-in-cardiac-neuron-excitability
#14
John D Tompkins, Todd A Clason, Thomas R Buttolph, Beatrice M Girard, Anne K Linden, Jean C Hardwick, Laura A Merriam, Victor May, Rodney L Parsons
Pituitary adenylate cyclase activating polypeptide (PACAP, Adcyap1) activation of PAC1 receptors (Adcyap1r1) significantly increases excitability of guinea pig cardiac neurons. This modulation of excitability is mediated in part by plasma membrane G protein-dependent activation of adenylyl cyclase and downstream signaling cascades. However, additional mechanisms responsible for the enhanced excitability are activated following internalization of the PAC1 receptor and endosomal signaling. Src family kinases play critical roles mediating endocytosis of many trophic factor and G-protein coupled receptors...
November 15, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29134605/p2y11-receptors-properties-distribution-and-functions
#15
Charles Kennedy
The P2Y11 receptor is a G protein-coupled receptor that is stimulated by endogenous purine nucleotides, particularly ATP. Amongst P2Y receptors it has several unique properties; (1) it is the only human P2Y receptor gene that contains an intron in the coding sequence; (2) the gene does not appear to be present in the rodent genome; (3) it couples to stimulation of both phospholipase C and adenylyl cyclase. Its absence in mice and rats, along with a limited range of selective pharmacological tools, has hampered the development of our knowledge and understanding of its properties and functions...
September 27, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29119630/mycobacterium-tuberculosis-rv3651-is-a-triple-sensor-domain-protein
#16
Jan Abendroth, Andrew Frando, Isabelle Q Phan, Bart L Staker, Peter J Myler, Thomas E Edwards, Christoph Grundner
The genome of the human pathogen Mycobacterium tuberculosis (Mtb) encodes ∼4,400 proteins, but one third of them have unknown functions. We solved the crystal structure of Rv3651, a hypothetical protein with no discernible similarity to proteins with known function. Rv3651 has a three-domain architecture that combines one cGMP-specific phosphodiesterases, adenylyl cyclases and FhlA (GAF) domain and two Per-ARNT-Sim (PAS) domains. GAF and PAS domains are typically sensor domains that are linked to signaling effector molecules...
November 9, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/29112589/androgens-mediate-%C3%AE-adrenergic-vasorelaxation-impairment-via-adenylyl-cyclase
#17
O A López-Canales, M C Castillo-Hernández, H Vargas-Robles, A Rios, J S López-Canales, B Escalante
Cardiovascular disease development has been associated with gender differences, suggesting that sex hormones are implicated in vascular function and development of hypertension. Vascular tone comparison at different stages of rat growth represents a good model to study testosterone-related vascular response. We explored the role of testosterone in modulation of age-dependent impaired β-adrenergic vasodilation.The 3 week-old male Sprague-Dawley rats were sorted in 3 week-old rats without any manipulation and 3 week-old rats treated with testosterone...
October 31, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/29108990/laminin-1-induces-endocytosis-of-67kda-laminin-receptor-and-protects-neuroscreen-1-cells-against-death-induced-by-serum-withdrawal
#18
Rayudu Gopalakrishna, Usha Gundimeda, Sarah Zhou, Helena Bui, Andrew Davis, Thomas McNeill, William Mack
Although the function of laminin in the basement membrane is known, the function of soluble "neuronal" laminin is unknown. Since laminin is neuroprotective, we determined whether the soluble laminin-1 induces signaling for neuroprotection via its 67KDa laminin-1 receptor (67LR). Treatment of Neuroscreen-1 (NS-1) cells with laminin-1 or YIGSR peptide, which corresponds to a sequence in laminin-1 β1 chain that binds to 67LR, induced a decrease in the cell-surface expression of 67LR and caused its internalization...
November 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29102625/reprint-of-role-of-g-protein-coupled-estrogen-receptor-gper-gpr30-in-maintenance-of-meiotic-arrest-in-fish-oocytes
#19
REVIEW
Peter Thomas
An essential role for GPER (formerly known as GPR30) in regulating mammalian reproduction has not been identified to date, although it has shown to be involved in the regulation a broad range of other estrogen-dependent functions. In contrast, an important reproductive role for GPER in the maintenance of oocyte meiotic arrest has been identified in teleost fishes, which is briefly reviewed here. Recent studies have clearly shown that ovarian follicle production of estradiol-17β (E2) maintains meiotic arrest in several teleost species through activation of GPER coupled to a stimulatory G protein (Gs) on oocyte plasma membranes, resulting in stimulation of cAMP production and maintenance of elevated cAMP levels...
November 2, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29101164/mathematical-modeling-physiological-effects-of-the-overexpression-of-%C3%AE-2-adrenoceptors-in-mouse-ventricular-myocytes
#20
Kelvin Rozier, Vladimir E Bondarenko
Transgenic (TG) mice overexpressing β2-adrenergic receptors (β2-ARs) demonstrate enhanced myocardial function, which manifests in increased basal adenylyl cyclase activity, enhanced atrial contractility, and increased left ventricular function in vivo. To gain insights into the mechanisms of these effects, we developed a comprehensive mathematical model of the mouse ventricular myocyte overexpressing β2-ARs. We found that most of the β2-ARs are active in control conditions in TG mice. Simulations describe the dynamics of major signaling molecules in different subcellular compartments; increased basal adenylyl cyclase activity; modifications of action potential shape and duration; the effects on the L-type Ca(2+) current and [Ca(2+)]i transients upon stimulation of β2-ARs in control, after the application of pertussis toxin (PTX), upon stimulation with a specific β2-AR agonist zinterol, and upon stimulation with zinterol in the presence of PTX...
November 3, 2017: American Journal of Physiology. Heart and Circulatory Physiology
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