Multinucleation of the sodC-Deficient Dictyostelium discoideum

Tsuji, Atsushi B.; Akaza, Yuya; Nakamura, Shōgo; Kodaira, Ken-Ichi; Yasukawa, Hiro

doi:10.1248/bpb.26.1174

Cited by 4 publications

(5 citation statements)

References 12 publications

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“…However, long-term growth on Klebsiella can cause upregulation of NoxB in growing cells ( 136 ). Interestingly, D. discoideum expresses multiple SOD and catalase homologs ( 177 – 179 ) and exhibits a high resistance to oxidative stress ( 180 ), which suggests that it encounters internally and/or externally generated ROS regularly.…”

Section: Microbicidal Phagosomementioning

confidence: 99%

Eat Prey, Live: Dictyostelium discoideum As a Model for Cell-Autonomous Defenses

et al. 2018

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The soil-dwelling social amoeba Dictyostelium discoideum feeds on bacteria. Each meal is a potential infection because some bacteria have evolved mechanisms to resist predation. To survive such a hostile environment, D. discoideum has in turn evolved efficient antimicrobial responses that are intertwined with phagocytosis and autophagy, its nutrient acquisition pathways. The core machinery and antimicrobial functions of these pathways are conserved in the mononuclear phagocytes of mammals, which mediate the initial, innate-immune response to infection. In this review, we discuss the advantages and relevance of D. discoideum as a model phagocyte to study cell-autonomous defenses. We cover the antimicrobial functions of phagocytosis and autophagy and describe the processes that create a microbicidal phagosome: acidification and delivery of lytic enzymes, generation of reactive oxygen species, and the regulation of Zn2+, Cu2+, and Fe2+ availability. High concentrations of metals poison microbes while metal sequestration inhibits their metabolic activity. We also describe microbial interference with these defenses and highlight observations made first in D. discoideum. Finally, we discuss galectins, TNF receptor-associated factors, tripartite motif-containing proteins, and signal transducers and activators of transcription, microbial restriction factors initially characterized in mammalian phagocytes that have either homologs or functional analogs in D. discoideum.

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Section: Microbicidal Phagosomementioning

confidence: 99%

Eat Prey, Live: Dictyostelium discoideum As a Model for Cell-Autonomous Defenses

et al. 2018

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“…SodC message is expressed both in vegetative and aggregative stages, and gradually declined as cells terminally differentiate (Van Driessche et al, 2002;Iranfar et al, 2003). Sequence analysis of SodC revealed a signal peptide as previously suggested (Tsuji et al, 2003), and a previously undescribed C-terminal glycosylphosphatidylinositol (GPI)-anchoring motif ( Fig. 2A).…”

Section: Identification and Characterization Of Sodcmentioning

confidence: 73%

“…Remi56, as well as three other mutants had insertions at the same locus encoding an extracellular superoxide dismutase (SOD) previously identified as SodC (Tsuji et al, 2003). SodC message is expressed both in vegetative and aggregative stages, and gradually declined as cells terminally differentiate (Van Driessche et al, 2002;Iranfar et al, 2003).…”

Section: Identification and Characterization Of Sodcmentioning

confidence: 99%

The GPI-anchored superoxide dismutase SodC is essential for regulating basal Ras activity and for chemotaxis of Dictyostelium discoideum

Veeranki

Kim

2008

Journal of Cell Science

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A genetic screen for Dictyostelium mutant displaying high level of constitutive phosphatidylinositol (3,4,5)-trisphosphate led to the finding that the glycosylphosphatidylinositol (GPI)-anchored superoxide dismutase SodC regulates small GTPase Ras. Cells that lack SodC exhibited constitutively high levels of active Ras, more membrane localization of GFP-PHcrac, and defects in chemoattractant sensing, cell polarization and motility. These defects of SodC-lacking cells were partially restored by expression of wild-type SodC but not by the catalytically inactive mutant SodC (H245R, H247Q). Furthermore, an inhibition of PI3K activity in SodC-deficient cells by LY294002 only partially restored chemoattractant sensing and cell polarization, consistent with the fact that SodC-deficient cells have aberrantly high level of active Ras, which functions upstream of PI3K. A higher level of active GFP-RasG was observed in SodC-deficient cells, which significantly decreased upon incubation of SodC-deficient cells with the superoxide scavenger XTT. Having constitutively high levels of active Ras proteins and more membrane localization of GFP-PHcrac, SodC-deficient cells exhibited severe defects in chemoattractant sensing, cell polarization and motility.

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“…The sequences for the sodA, sodB, (Tsuji et al, 2002) and sodC (Tsuji et al, 2003) genes suggest that they are Cu/Zn enzymes. The sodA and sodB proteins both contain charged amino acids and hydrophobic stretches in the N-termini suggesting that they are extracellular.…”

Section: Antioxidant Defense Mechanisms In D Discoideummentioning

confidence: 99%

“…Studies on D. discoideum sodC showed that expression decreased in the presence of H2O2 and that sodC null cells were multinucleate although the meaning of this was not investigated (Tsuji et al, 2003) and that sodC regulates the small GTPase RAS. D. discoideum sodC null cells have constitutively high activation of Ras, and sodC null cells treated with the scavenger XTT reduced the up-regulation of Ras (Veeranki et al, 2008).…”

Section: Antioxidant Defense Mechanisms In D Discoideummentioning

confidence: 99%

Curcumin regulates transcription in Dictyostelium discoideum

Swatson¹,

William²

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Botanicals are widely used as dietary supplements and for the prevention and treatment of a myriad of diseases ranging from the common cold to depression. One in four Americans uses a botanical as part of their primary healthcare with billions of dollars spent annually. Curcumin, the active ingredient in turmeric, has gained a lot attention in recent years for its therapeutic uses and has been linked to a wide spectrum of pharmacological effects including anti-carcinogenic, anti-inflammatory, Alzheimer's prevention and antioxidant activity. Despite the large and growing interest in the use of botanicals such as curcumin in disease treatment and prevention, there is little evidence regarding their efficacy, safety and long-term effects. Importantly, the fundamental mechanisms associated with the cellular response to botanicals are generally not clearly understood, and there are often unknown off-target effects. This is supported by the bafflingly large number of effects associated with curcumin. The use of suitable model systems in pharmacogenetic analysis allows for the subsequent characterization of genes and their protein products to explain the mechanisms of drug action. Understanding the complex mechanisms associated with drug response is compounded by the use of mammalian models. In addition, the maintenance and care of such models, the large numbers of animals required for experimental study as well as ethical concerns have necessitated the use of simple and genetically tractable non-mammalian models. The social amoeba, Dictyostelium discoideum, has proven to be an excellent model for the molecular and genetic study of the mechanisms of action of drugs and their effects on the cell. D discoideum has been successfully used to find targets to improve efficacy of drugs used in psychiatry and cancer treatment. Those studies were subsequently validated in human cells. By taking advantage of this simple but powerful biological model and the molecular genetic tools available to us, we have started to investigate the complex effects of the botanical compound curcumin on cell growth, cell physiology and the underlying molecular mechanisms of action. Results from our studies revealed a rather complex pleiotropic response to curcumin including effects on proliferation, oxidative stress and a global regulation of gene expression at the transcriptional level. The relative lack of conclusive scientific evidence regarding the therapeutic benefits of curcumin, coupled with curcumin's possible deleterious effects as revealed by our research findings, underscore the importance of further research to establish curcumin's risks and benefits. Ascertaining the risk-benefits of curcumin with more conclusive scientific evidence would better equip consumers to make decisions about using curcumin, and in fact other botanicals, as part of their primary healthcare.

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Multinucleation of the sodC-Deficient Dictyostelium discoideum

Cited by 4 publications

References 12 publications

Eat Prey, Live: Dictyostelium discoideum As a Model for Cell-Autonomous Defenses

Eat Prey, Live: Dictyostelium discoideum As a Model for Cell-Autonomous Defenses

The GPI-anchored superoxide dismutase SodC is essential for regulating basal Ras activity and for chemotaxis of Dictyostelium discoideum

Curcumin regulates transcription in Dictyostelium discoideum

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