Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.3.16 (calcineurin)
17,112 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Hog1 mitogen-activated protein (MAP) kinase mediates an adaptive response to both osmotic and oxidative stress in the fungal pathogen Candida albicans. This protein also participates in two distinct morphogenetic processes, namely the yeast-to-hypha transition (as a repressor) and chlamydospore formation (as an inducer). We show here that repression of filamentous growth occurs both under serum limitation and under other partially inducing conditions, such as low temperature, low pH, or nitrogen starvation. To understand the relationship of the HOG pathway to other MAP kinase cascades that also play a role in morphological transitions, we have constructed and characterized a set of double mutants in which we deleted both the HOG1 gene and other signaling elements (the CST20, CLA4, and HST7 kinases, the CPH1 and EFG1 transcription factors, and the CPP1 protein phosphatase). We also show that Hog1 prevents the yeast-to-hypha switch independent of all the elements analyzed and that the inability of the hog1 mutants to form chlamydospores is suppressed when additional elements of the CEK1 pathway (CST20 or HST7) are altered. Finally, we report that Hog1 represses the activation of the Cek1 MAP kinase under basal conditions and that Cek1 activation correlates with resistance to certain cell wall inhibitors (such as Congo red), demonstrating a role for this pathway in cell wall biogenesis.
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PMID:The Cek1 and Hog1 mitogen-activated protein kinases play complementary roles in cell wall biogenesis and chlamydospore formation in the fungal pathogen Candida albicans. 1646 75

How learning and memory is controlled at the neural circuit level is a fundamental question in neuroscience. However, molecular and cellular dissection of the neural circuits underlying learning and memory is extremely complicated in higher animals. Here, we report a simple neural circuit for learning behavior in Caenorhabditis elegans, where the calcium-activated phosphatase, calcineurin, acts as an essential modulator. The calcineurin mutant tax-6 showed defective feeding state-dependent learning behavior for temperature and salt. Surprisingly, defective associative learning between temperature and feeding state was caused by malfunctions of two pairs of directly connected interneurons, AIZ and RIA, in the mature nervous system. Monitoring temperature-evoked Ca2+ concentration changes in the AIZ-RIA neural pathway revealed that starvation, a conditioning factor, downregulated AIZ activity through calcineurin during associative learning between temperature and feeding state. Our results demonstrate the molecular and physiological mechanisms of a simple neural circuit for calcineurin-mediated associative learning behavior.
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PMID:Molecular physiology of the neural circuit for calcineurin-dependent associative learning in Caenorhabditis elegans. 1697 19

To learn about the cellular processes involved in Mg(2+) homeostasis and the mechanisms allowing cells to cope with low Mg(2+) availability, we performed RNA expression-profiling experiments and followed changes in gene activity upon Mg(2+) depletion on a genome-wide scale. A striking portion of genes up-regulated under Mg(2+) depletion are also induced by high Ca(2+) and/or alkalinization. Among the genes significantly up-regulated by Mg(2+) starvation, Ca(2+) stress, and alkalinization are ENA1 (encoding a P-type ATPase sodium pump) and PHO89 (encoding a sodium/phosphate cotransporter). We show that up-regulation of these genes is dependent on the calcineurin/Crz1p (calcineurin-responsive zinc finger protein) signaling pathway. Similarly to Ca(2+) stress, Mg(2+) starvation induces translocation of the transcription factor Crz1p from the cytoplasm into the nucleus. The up-regulation of ENA1 and PHO89 upon Mg(2+) starvation depends on extracellular Ca(2+). Using fluorescence resonance energy transfer microscopy, we demonstrate that removal of Mg(2+) results in an immediate increase in free cytoplasmic Ca(2+). This effect is dependent on external Ca(2+). The results presented indicate that Mg(2+) depletion in yeast cells leads to enhanced cellular Ca(2+) concentrations, which activate the Crz1p/calcineurin pathway. We provide evidence that calcineurin/Crz1p signaling is crucial for yeast cells to cope with Mg(2+) depletion stress.
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PMID:Mg2+ deprivation elicits rapid Ca2+ uptake and activates Ca2+/calcineurin signaling in Saccharomyces cerevisiae. 1733 37

The antiarrhythmic drug amiodarone has fungicidal activity against a broad range of fungi. In Saccharomyces cerevisiae, it elicits an immediate influx of Ca(2+) followed by mitochondrial fragmentation and eventual cell death. To dissect the mechanism of its toxicity, we assessed the transcriptional response of S. cerevisiae to amiodarone by DNA microarray. Consistent with the drug-induced calcium burst, more than half of the differentially transcribed genes were induced by high levels of CaCl(2). Amiodarone also caused rapid nuclear accumulation of the calcineurin-regulated Crz1. The majority of genes induced by amiodarone within 10 min were involved in utilization of alternative carbon and nitrogen sources and in mobilizing energy reserves. The similarity to nutrient starvation responses seen in stationary phase cells, rapamycin treatment, and late stages of shift to diauxic conditions and nitrogen depletion suggests that amiodarone may interfere with nutrient sensing and regulatory networks. Transcription of a set of nutrient-responsive genes was affected by amiodarone but not CaCl(2), indicating that activation of the starvation response was independent of Ca(2+). Genes down-regulated by amiodarone were involved in all stages of cell cycle control. A moderate dose of amiodarone temporarily delayed cell cycle progression at G(1), S, and G(2)/M phases, with the Swe1-mediated delay in G(2)/M phase being most prominent in a calcineurin-dependent manner. Overall, the transcriptional responses to amiodarone revealed by this study were found to be distinct from other classes of antifungals, including the azole drugs, pointing toward a novel target pathway in combating fungal pathogenesis.
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PMID:Global disruption of cell cycle progression and nutrient response by the antifungal agent amiodarone. 1797 66

Thermotactic behavior in the nematode Caenorhabditis elegans exhibits long-term plasticity. On a spatial thermal gradient, C. elegans tracks isotherms near a remembered set-point (T(S)) corresponding to its previous cultivation temperature. When navigating at temperatures above its set-point (T>T(S)), C. elegans crawls down spatial thermal gradients towards the T(S) in what is called cryophilic movement. The T(S) retains plasticity in the adult stage and is reset by approximately 4 h of sustained exposure to a new temperature. Long-term plasticity in C. elegans thermotactic behavior has been proposed to represent an associative learning of specific temperatures conditioned in the presence or absence of bacterial food. Here, we use quantitative behavioral assays to define the temperature and food-dependent determinants of long-term plasticity in the different modes of thermotactic behavior. Under our experimental conditions, we find that starvation at a specific temperature neither disrupts T(S) resetting toward the starvation temperature nor induces learned avoidance of the starvation temperature. We find that prolonged starvation suppresses the cryophilic mode of thermotactic behavior. The hen-1 and tax-6 genes have been reported to affect associative learning between temperature and food-dependent cues. Under our experimental conditions, mutation in the hen-1 gene, which encodes a secreted protein with an LDL receptor motif, does not significantly affect thermotactic behavior or long-term plasticity. Mutation in the tax-6 calcineurin gene abolishes thermotactic behavior altogether. In summary, we do not find evidence that long-term plasticity requires association between temperature and the presence or absence of bacterial food.
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PMID:Temperature and food mediate long-term thermotactic behavioral plasticity by association-independent mechanisms in C. elegans. 1798 72

The PHO1 protein is involved in loading inorganic phosphate (Pi) to the root xylem. Ten genes homologous to AtPHO1 are present in the Arabidopsis thaliana (L.) Heyn genome. From this gene family, transcript levels of only AtPHO1, AtPHO1;H1 and AtPHO1;H10 were increased by Pi-deficiency. While the up-regulation of AtPHO1;H1 and AtPHO1;H10 by Pi deficiency followed the same rapid kinetics and was dependent on the PHR1 transcription factor, phosphite only strongly suppressed the expression of AtPHO1;H1 and had a minor effect on AtPHO1;H10. Addition of sucrose was found to increase transcript levels of both AtPHO1 and AtPHO1;H1 in Pi-sufficient or Pi-deficient plants, but to suppress AtPHO1:H10 under the same conditions. Treatments of plants with auxin or cytokinin had contrasting effect depending on the gene and on the Pi status of the plants. Thus, while both hormones down-regulated expression of AtPHO1 independently of the plant Pi status, auxin and cytokinin up-regulated AtPHO1;H1 and AtPHO1;H10 expression in Pi-sufficient plants and down-regulated expression in Pi-deficient plants. Treatments with abscisic acid inhibited AtPHO1 and AtPHO1;H1 expression in both Pi-sufficient and Pi-deficient plants, but increased AtPHO1;H10 expression under the same conditions. The inhibition of expression by abscisic acid of AtPHO1 and AtPHO1;H1, and of the Pi-starvation responsive genes AtPHT1;1 and AtIPS1, was dependant on the ABI1 type 2C protein phosphatase. These results reveal that various levels of cross talk between the signal transduction pathways to Pi, sucrose and phytohormones are involved in the regulation of expression of the three AtPHO1 homologues.
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PMID:Expression analyses of three members of the AtPHO1 family reveal differential interactions between signaling pathways involved in phosphate deficiency and the responses to auxin, cytokinin, and abscisic acid. 1809 93

Glucokinase (GK, hexokinase type IV) is required for the accumulation of glycogen in adult liver and hepatoma cells. Paradoxically, mammalian embryonic livers store glycogen successfully in the absence of GK. Here we address how mammalian embryonic livers, but not adult livers or hepatoma cells, manage to accumulate glycogen in the absence of this enzyme. Hexokinase type I or II (HKI, HKII) substitutes for GK in hepatomas and in embryonic livers. We engineered FTO2B cells, a hepatoma cell line in which GK is not expressed, to unveil the modifications required to allow them to accumulate glycogen. In the light of these results, we then examined glycogen metabolism in embryonic liver. Glycogen accumulation in FTO2B cells can be triggered through elevated expression of HKI or either of the protein phosphatase 1 regulatory subunits, namely PTG or G L. Between these two strategies to activate glycogen deposition in the absence of GK, embryonic livers choose to express massive levels of HKI and HKII. We conclude that although the GK/liver glycogen synthase tandem is ideally suited to store glycogen in liver when blood glucose is high, the substitution of HKI for GK in embryonic livers allows the HKI/liver glycogen synthase tandem to make glycogen independently of the glucose concentration in blood, although it requires huge levels of HK. Moreover, the physiological consequence of the HK isoform switch is that the embryonic liver safeguards its glycogen deposits, required as the main source of energy at birth, from maternal starvation.
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PMID:Hepatic glycogen synthesis in the absence of glucokinase: the case of embryonic liver. 1816 36

The control of potassium (K+) acquisition is a critical requirement for plant growth. Although HAK1 (high affinity K+ 1) transporters provide a pathway for K+ acquisition, the effect exerted by the ionic environment on their contribution to K+ capture remains essentially unknown. Here, the influence of the ionic environment on the accumulation of transcripts coding for the barley (Hordeum vulgare) HvHAK1 transporter as well as on HvHAK1-mediated K+ capture has been examined. In situ mRNA hybridization studies show that HvHAK1 expression occurs in most root cells, being augmented at the outermost cell layers. Accumulation of HvHAK1 transcripts is enhanced by K+ deprivation and transiently by exposure to high salt concentrations. In addition, studies on the accumulation of transcripts coding for HvHAK1 and its close homolog HvHAK1b revealed the presence of two K+-responsive pathways, one repressed and the other insensitive to ammonium. Experiments with Arabidopsis (Arabidopsis thaliana) HvHAK1-expressing transgenic plants showed that K+ deprivation enhances the capture of K+ mediated by HvHAK1. A detailed study with HvHAK1-expressing Saccharomyces cerevisiae cells also revealed an increase of K+ uptake after K+ starvation. This increase did not occur in cells grown at high Na+ concentrations but took place for cells grown in the presence of NH4+. 3,3'-Dihexyloxacarbocyanine iodide accumulation measurements indicate that the increased capture of K+ in HvHAK1-expressing yeast cells cannot be explained only by changes in the membrane potential. It is shown that the yeast protein phosphatase PPZ1 as well as the halotolerance HAL4/HAL5 kinases negatively regulate the HvHAK1-mediated K+ transport.
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PMID:The ionic environment controls the contribution of the barley HvHAK1 transporter to potassium acquisition. 1835 46

A prerequisite of calcium signaling is the maintenance of cytoplasmic free Ca(2+) within a narrow, sub-micromolar range, compatible with cell viability. A variety of stress inducing agents and drugs can lead to a disruption of calcium homeostasis with ensuing toxicity. Amiodarone, an anti-arrhythmic drug with broad range microbicidal effect, has been shown to trigger a calcium burst in the yeast Saccharomyces cerevisiae. Recently, we reported that amiodarone elicits a starvation response, blocks cell cycle progression at multiple stages and represses the transcription of cell cycle genes. Here, we examine the connections between Ca(2+)-calcineurin signaling, nutrient sensing and regulation of the cell cycle.
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PMID:A spoke in the wheel: calcium spikes disrupt yeast cell cycle. 1841 24

Adaptation of plants to phosphate (Pi) deficiency is a complex process involving host of biochemical changes. These changes are integrated at transcriptional level by Pi starvation mediated signal transduction pathway. Many of the signaling processes are regulated by reversible protein phosphorylation directed by protein kinases and protein phosphatases. In this study, we report the characterization of a protein phosphatase gene (LePS2;1) from tomato induced during phosphate starvation. The bacterially expressed recombinant LePS2;1 protein readily dephosphorylated a synthetic phospho-Ser/Thr peptide. Okadaic acid, an inhibitor of Ser/Thr protein phosphatases, suppressed the enzyme activity. Western blot analysis revealed the Pi starvation dependent accumulation of LePS2;1 protein. Over-expression of LePS2;1 in tomato plants resulted in increased anthocyanin accumulation and acid phosphatase activity under Pi sufficient condition. Transgenic plants exhibited distinct changes in morphology and delayed flower initiation. These results provide evidence that the protein phosphatase LePS2;1, plays an important role in phosphate starvation induced processes in tomato. To our knowledge this is the first comprehensive analysis of a protein phosphatase induced during phosphate starvation.
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PMID:Biochemical and molecular analysis of LePS2;1: a phosphate starvation induced protein phosphatase gene from tomato. 1845 47


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