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P N Devreotes - One of the best experts on this subject based on the ideXlab platform.
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Cyclic AMP Receptors of dictyostelium
Reference Module in Biomedical Sciences#R##N#Encyclopedia of Biological Chemistry, 2013Co-Authors: D Hereld, Y Kamimura, P N DevreotesAbstract:When confronted with starvation, the social amoeba Dictyostelium discoideum survives by undergoing multicellular development and sporulation. The coordination of these processes is achieved in part through intercellular communication using secreted adenosine 3′,5′-Cyclic adenosine monophosphate (cAMP) and a family of cell-surface cAMP Receptors (cARs). The cARs are exAMPles of G-protein-coupled Receptors (GPCRs), which enable eukaryotic cells in general to sense and respond to a wide array of environmental and hormonal signals ranging from single photons to large glycoprotein hormones. Due to their involvement in diverse physiological processes, GPCR-targeted drugs are frequently employed in medicine to treat many common conditions, including inflammation, hypertension, heart failure, and neurologic and psychiatric disorders. Because GPCRs and the pathways they regulate are conserved in virtually all eukaryotes examined to date, genetically tractable microbes such as Dictyostelium have contributed significantly to our understanding of GPCR function and regulation.
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the surface Cyclic AMP Receptors car1 car2 and car3 promote ca2 influx in dictyostelium discoideum by a g alpha 2 independent mechanism
Molecular Biology of the Cell, 1993Co-Authors: Jacqueline L S Milne, P N DevreotesAbstract:Activation of surface folate Receptors or Cyclic AMP (cAMP) receptor (cAR) 1 in Dictyostelium triggers within 5-10 s an influx of extracellular Ca2+ that continues for 20 s. To further characterize the receptor-mediated Ca2+ entry, we analyzed 45Ca2+ uptake in amoebas overexpressing cAR2 or cAR3, cARs present during multicellular development. Both Receptors induced a cAMP-dependent Ca2+ uptake that had comparable kinetics, ion selectivity, and inhibitor profiles as folate- and cAR1-mediated Ca2+ uptake. Analysis of mutants indicated that receptor-induced Ca2+ entry does not require G protein alpha subunits G alpha 1, G alpha 2, G alpha 3, G alpha 4, G alpha 7, or G alpha 8. Overexpression of cAR1 or cAR3 in g alpha 2- cells did not restore certain G alpha 2-dependent events, such as aggregation, or cAMP-mediated activation of adenylate and guanylate cyclases, but these strains displayed a cAMP-mediated Ca2+ influx with kinetics comparable to wild-type aggregation-competent cells. These results suggest that a plasma membrane-associated Ca(2+)-influx system may be activated by at least four distinct chemoReceptors during Dictyostelium development and that the response may be independent of G proteins.
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multiple Cyclic AMP Receptors are linked to adenylyl cyclase in dictyostelium
Molecular Biology of the Cell, 1992Co-Authors: Maureen Pupillo, Robert H Insall, Geoffrey S Pitt, P N DevreotesAbstract:cAMP receptor 1 and G-protein alpha-subunit 2 null cell lines (car1- and g alpha 2-) were examined to assess the roles that these two proteins play in cAMP stimulated adenylyl cyclase activation in Dictyostelium. In intact wild-type cells, cAMP stimulation elicited a rapid activation of adenylyl cyclase that peaked in 1-2 min and subsided within 5 min; in g alpha 2- cells, this activation did not occur; in car1- cells an activation occurred but it rose and subsided more slowly. cAMP also induced a persistent activation of adenylyl cyclase in growth stage cells that contain only low levels of cAMP receptor 1 (cAR1). In lysates of untreated wild-type, car1-, or g alpha 2- cells, guanosine 5'-O-'(3-thiotriphosphate) (GTP gamma S) produced a similar 20-fold increase in adenylyl cyclase activity. Brief treatment of intact cells with cAMP reduced this activity by 75% in control and g alpha 2- cells but by only 8% in the car1- cells. These observations suggest several conclusions regarding the cAMP signal transduction system. 1) cAR1 and another cAMP receptor are linked to activation of adenylyl cyclase in intact cells. Both excitation signals require G alpha 2. 2) cAR1 is required for normal adaptation of adenylyl cyclase. The adaptation reaction caused by cAR1 is not mediated via G alpha 2. 3) Neither cAR1 nor G alpha 2 is required for GTP gamma S-stimulation of adenylyl cyclase in cell lysates. The adenylyl cyclase is directly coupled to an as yet unidentified G-protein.
Peter C. Newell - One of the best experts on this subject based on the ideXlab platform.
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Signal transduction and motility ofDictyostelium
Bioscience Reports, 1995Co-Authors: Peter C. NewellAbstract:This review is concerned with the roles of Cyclic GMP and Ca^2+ ions in signal transduction for chemotaxis of Dictyostelium . These molecules are involved in signalling between the cell surface Cyclic AMP Receptors and cytoskeletal myosin II involved in chemotactic cell movement. Evidence is presented for uptake and/or eflux of Ca^2+ being regulated by Cyclic GMP. The link between Ca^2+, Cyclic GMP and chemotactic cell movement has been explored using “streamer F” mutants whose primary defect is in the structural gene for the Cyclic GMP-specific phosphodiesterase. This mutation causes the mutants to produce an abnormally prolonged peak of Cyclic GMP accumulation in response to stimulation with the chemoattractant Cyclic AMP. The production and relay of Cyclic AMP signals is normal in these mutants, but certain events associated with movement are (like the Cyclic GMP response) abnormally prolonged in the mutants. These events include Ca^2+ uptake, myosin II association with the cytoskeleton and regulation of both myosin heavy and light chain phosphorylation. These changes can be correlated with changes in the shape of the amoebae after chemotactic stimulation. Other mutants in which the accumulation of Cyclic GMP in response to Cyclic AMP stimulation was absent produced no myosin II responses. A model is described in which Cyclic GMP (directly or indirectly via Ca^2+) regulates accumulation of myosin II on the cytoskeleton by regulating phosphorylation of the myosin heavy and light chain kinases.
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Calcium, Cyclic GMP and the control of myosin II during chemotactic signal transduction ofDictyostelium
Journal of Biosciences, 1995Co-Authors: Peter C. NewellAbstract:Evidence is presented for Ca^2+ and Cyclic GMP being involved in signal transduction between the cell surface Cyclic AMP Receptors and cytoskeletal myosin II involved in chemotactic cell movement. Ca^2+ is shown to be required for chemotactic aggregation of amoebae. The evidence for uptake and/or eflux of this ion being regulated by the nucleotide Cyclic GMP is discussed. The connection between Ca^2+, Cyclic GMP and chemotactic cell movement has been explored using “streamer F” mutants. The primary defect in these mutants is in the structural gene for the Cyclic GMP-specific phosphodiesterase which results in the mutants producing an abnormally prolonged peak of accumulation of Cyclic GMP in response to stimulation with the chernoattractant Cyclic AMP. While events associated with production and relay of Cyclic AMP signals are normal, certain events associated with movement are (like the Cyclic GMP response) abnormally prolonged in the mutants. These events include Ca^2+ uptake, myosin II association with the cytoskeleton and inhibition of myosin heavy and light chain phosphorylation. These changes can be correlated with the amoebae becoming elongated and transiently decreasing their locomotive speed after chemotactic stimulation. Other mutants studied in which the accumulation of Cyclic GMP in response to Cyclic AMP stimulation was absent produced no myosin II responses. Models are described in which Cyclic GMP (directly or indirectly via Ca^2+) regulates accumulation of myosin II on the cytoskeleton by inhibiting phosphorylation of the myosin heavy and light chain kinases.
Maureen Pupillo - One of the best experts on this subject based on the ideXlab platform.
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multiple Cyclic AMP Receptors are linked to adenylyl cyclase in dictyostelium
Molecular Biology of the Cell, 1992Co-Authors: Maureen Pupillo, Robert H Insall, Geoffrey S Pitt, P N DevreotesAbstract:cAMP receptor 1 and G-protein alpha-subunit 2 null cell lines (car1- and g alpha 2-) were examined to assess the roles that these two proteins play in cAMP stimulated adenylyl cyclase activation in Dictyostelium. In intact wild-type cells, cAMP stimulation elicited a rapid activation of adenylyl cyclase that peaked in 1-2 min and subsided within 5 min; in g alpha 2- cells, this activation did not occur; in car1- cells an activation occurred but it rose and subsided more slowly. cAMP also induced a persistent activation of adenylyl cyclase in growth stage cells that contain only low levels of cAMP receptor 1 (cAR1). In lysates of untreated wild-type, car1-, or g alpha 2- cells, guanosine 5'-O-'(3-thiotriphosphate) (GTP gamma S) produced a similar 20-fold increase in adenylyl cyclase activity. Brief treatment of intact cells with cAMP reduced this activity by 75% in control and g alpha 2- cells but by only 8% in the car1- cells. These observations suggest several conclusions regarding the cAMP signal transduction system. 1) cAR1 and another cAMP receptor are linked to activation of adenylyl cyclase in intact cells. Both excitation signals require G alpha 2. 2) cAR1 is required for normal adaptation of adenylyl cyclase. The adaptation reaction caused by cAR1 is not mediated via G alpha 2. 3) Neither cAR1 nor G alpha 2 is required for GTP gamma S-stimulation of adenylyl cyclase in cell lysates. The adenylyl cyclase is directly coupled to an as yet unidentified G-protein.
Antoine Danchin - One of the best experts on this subject based on the ideXlab platform.
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bifunctional structure of two adenylyl cyclases from the myxobacterium stigmatella aurantiaca
Biochimie, 1997Co-Authors: M P Coudartcavalli, Odile Sismeiro, Antoine DanchinAbstract:Abstract Two adenylyl cyclase genes (cyaA and cyaB) from the myxobacterium Stigmatella aurantiaca were cloned by complementation of Escherichia coli mutants defective in the cya gene. cyaA codes for a protein of 424 amino acid residues (AC1), while cyaB encodes a protein of 352 residues (AC2). Both cyclases are sensitive to adenosine: cAMP production was strongly inhibited in E coli cells and cell extracts expressing these genes. AC1 comprises a hydrophobic domain of six transmembrane helices coupled to a cytoplasmic catalytic domain endowed with adenylyl cyclase activity. A 17 amino acid residue sequence, which is a signature of G-protein coupled Receptors, as well as of slime mold Dictyostelium discoideum Cyclic AMP Receptors, was found in the membrane domain. AC2 displays features also indicating that it is a bifunctional enzyme. The domain located upstream from the catalytic adenylyl cyclase domain shows strong similarity to receiver modules of response regulators of two-component bacterial signaling systems. In vitro mutagenesis of conserved aspartate residues in this domain was shown to interfere with cAMP synthesis.
Geoffrey S Pitt - One of the best experts on this subject based on the ideXlab platform.
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multiple Cyclic AMP Receptors are linked to adenylyl cyclase in dictyostelium
Molecular Biology of the Cell, 1992Co-Authors: Maureen Pupillo, Robert H Insall, Geoffrey S Pitt, P N DevreotesAbstract:cAMP receptor 1 and G-protein alpha-subunit 2 null cell lines (car1- and g alpha 2-) were examined to assess the roles that these two proteins play in cAMP stimulated adenylyl cyclase activation in Dictyostelium. In intact wild-type cells, cAMP stimulation elicited a rapid activation of adenylyl cyclase that peaked in 1-2 min and subsided within 5 min; in g alpha 2- cells, this activation did not occur; in car1- cells an activation occurred but it rose and subsided more slowly. cAMP also induced a persistent activation of adenylyl cyclase in growth stage cells that contain only low levels of cAMP receptor 1 (cAR1). In lysates of untreated wild-type, car1-, or g alpha 2- cells, guanosine 5'-O-'(3-thiotriphosphate) (GTP gamma S) produced a similar 20-fold increase in adenylyl cyclase activity. Brief treatment of intact cells with cAMP reduced this activity by 75% in control and g alpha 2- cells but by only 8% in the car1- cells. These observations suggest several conclusions regarding the cAMP signal transduction system. 1) cAR1 and another cAMP receptor are linked to activation of adenylyl cyclase in intact cells. Both excitation signals require G alpha 2. 2) cAR1 is required for normal adaptation of adenylyl cyclase. The adaptation reaction caused by cAR1 is not mediated via G alpha 2. 3) Neither cAR1 nor G alpha 2 is required for GTP gamma S-stimulation of adenylyl cyclase in cell lysates. The adenylyl cyclase is directly coupled to an as yet unidentified G-protein.
