Calcineurin Silencing in Dictyostelium discoideum Leads to Cellular Alterations Affecting Mitochondria, Gene Expression, and Oxidative Stress Response

Kobel-Höller, Konstanze; Gley, Kevin; Jochinke, Janina; Heider, Kristina; Fritsch, Verena Nadin; Nguyen, Ha Viet Duc; Lischke, Timo; Radek, Renate; Baumgrass, Ria; Mutzel, Rupert; Thewes, Sascha

doi:10.1016/j.protis.2018.04.004

Cited by 5 publications

(7 citation statements)

References 92 publications

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“…However, despite its role in a diversity of chemotactic events in other species, investigations into the role of CanA suggest it is not linked to folic acid‐mediated chemotaxis. Instead, it is critical to numerous other basic cellular processes essential for growth and, as detailed later, asexual development (Kobel‐Höller et al, ). However, CanA has been implicated in cAMP‐mediated chemotaxis, fitting with the results of Gauthier & O'Day (Gauthier & O'Day, ) who showed significant differences in the CaMBP profiles of cells capable of folic acid‐mediated chemotaxis versus those undergoing cAMP‐mediated chemotaxis.…”

Section: Cell Motility and Chemotaxis During Growthsupporting

confidence: 82%

Calmodulin‐mediated events during the life cycle of the amoebozoan Dictyostelium discoideum

et al. 2019

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This review focusses on the functions of intracellular and extracellular calmodulin, its target proteins and their binding proteins during the asexual life cycle of Dictyostelium discoideum. Calmodulin is a primary regulatory protein of calcium signal transduction that functions throughout all stages. During growth, it mediates autophagy, the cell cycle, folic acid chemotaxis, phagocytosis, and other functions. During mitosis, specific calmodulin‐binding proteins translocate to alternative locations. Translocation of at least one cell adhesion protein is calmodulin dependent. When starved, cells undergo calmodulin‐dependent chemotaxis to cyclic AMP generating a multicellular pseudoplasmodium. Calmodulin‐dependent signalling within the slug sets up a defined pattern and polarity that sets the stage for the final events of morphogenesis and cell differentiation. Transected slugs undergo calmodulin‐dependent transdifferentiation to re‐establish the disrupted pattern and polarity. Calmodulin function is critical for stalk cell differentiation but also functions in spore formation, events that begin in the pseudoplasmodium. The asexual life cycle restarts with the calmodulin‐dependent germination of spores. Specific calmodulin‐binding proteins as well as some of their binding partners have been linked to each of these events. The functions of extracellular calmodulin during growth and development are also discussed. This overview brings to the forefront the central role of calmodulin, working through its numerous binding proteins, as a primary downstream regulator of the critical calcium signalling pathways that have been well established in this model eukaryote. This is the first time the function of calmodulin and its target proteins have been documented through the complete life cycle of any eukaryote.

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Section: Cell Motility and Chemotaxis During Growthsupporting

confidence: 82%

Calmodulin‐mediated events during the life cycle of the amoebozoan Dictyostelium discoideum

et al. 2019

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“…Only a few inhibitors of specific CaMBPs have been identified and studied in Dictyostelium. The immunosuppressant cyclosporin and FK508 were used in early studies revealing the importance of calcineurin in asexual development, work that has continued on this central CaMBP [54,55].…”

Section: Calmodulin Antagonists Provide Some Insightmentioning

confidence: 99%

Calmodulin and Calmodulin Binding Proteins in Dictyostelium: A Primer

O’Day

Taylor

Myre

2020

IJMS

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Dictyostelium discoideum is gaining increasing attention as a model organism for the study of calcium binding and calmodulin function in basic biological events as well as human diseases. After a short overview of calcium-binding proteins, the structure of Dictyostelium calmodulin and the conformational changes effected by calcium ion binding to its four EF hands are compared to its human counterpart, emphasizing the highly conserved nature of this central regulatory protein. The calcium-dependent and -independent motifs involved in calmodulin binding to target proteins are discussed with examples of the diversity of calmodulin binding proteins that have been studied in this amoebozoan. The methods used to identify and characterize calmodulin binding proteins is covered followed by the ways Dictyostelium is currently being used as a system to study several neurodegenerative diseases and how it could serve as a model for studying calmodulinopathies such as those associated with specific types of heart arrythmia. Because of its rapid developmental cycles, its genetic tractability, and a richly endowed stock center, Dictyostelium is in a position to become a leader in the field of calmodulin research.

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“…A similarly rounded mitochondrial phenotype with increased content of mitochondrial DNA was observed in calcineurin-silenced vegetative cells in D. discoideum, which was speculated to be associated with oxidative stress. 54 To verify, the authors assessed gene expression in several oxidative stress-related genes (sodA, sodB, sodC, sod2, and catA) and reported an upregulation in all but one of the measured genes. This indicates that increased intracellular oxidative stress was a result of calcineurin silencing.…”

Section: Ipta-deficiency and Overexpression Downregulates Amino Acid ...mentioning

confidence: 99%

“…It was concluded that calcineurin is involved in the interplay between mitochondria and reactive oxygen species in vegetative growth in D. discoideum. 54 While we did not assess redox metabolites beyond NAD + and NADH, there are numerous reports on the protective effects of CKs against oxidative stress in mammalian cells, 55,56 plants, [57][58][59][60] and bacteria. 61,62 Taken together, it would be of interest to assess oxidative stress in the iptA-deficient and overexpression strains to determine whether CK and/or IptA exerts any protective effects in D. discoideum.…”

Section: Ipta-deficiency and Overexpression Downregulates Amino Acid ...mentioning

confidence: 99%

From biosynthesis and beyond—Loss or overexpression of the cytokinin synthesis gene, iptA, alters cytokinesis and mitochondrial and amino acid metabolism in Dictyostelium discoideum

Aoki,

Kisiala,

Mathavarajah

et al. 2023

The FASEB Journal

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Cytokinins (CKs) are a class of growth‐promoting signaling molecules that affect multiple cellular and developmental processes. These phytohormones are well studied in plants, but their presence continues to be uncovered in organisms spanning all kingdoms, which poses new questions about their roles and functions outside of plant systems. Cytokinin production can be initiated by one of two different biosynthetic enzymes, adenylate isopentenyltransfases (IPTs) or tRNA isopentenyltransferases (tRNA‐IPTs). In this study, the social amoeba, Dictyostelium discoideum, was used to study the role of CKs by generating deletion and overexpression strains of its single adenylate‐IPT gene, iptA. The life cycle of D. discoideum is unique and possesses both single‐ and multicellular stages. Vegetative amoebae grow and divide while food resources are plentiful, and multicellular development is initiated upon starvation, which includes distinct life cycle stages. CKs are produced in D. discoideum throughout its life cycle and their functions have been well studied during the later stages of multicellular development of D. discoideum. To investigate potential expanded roles of CKs, this study focused on vegetative growth and early developmental stages. We found that iptA‐deficiency results in cytokinesis defects, and both iptA‐deficiency and overexpression results in dysregulated tricarboxylic acid (TCA) cycle and amino acid metabolism, as well as increased levels of adenosine monophosphate (AMP). Collectively, these findings extend our understanding of CK function in amoebae, indicating that iptA loss and overexpression alter biological processes during vegetative growth that are distinct from those reported during later development.

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Calcineurin Silencing in Dictyostelium discoideum Leads to Cellular Alterations Affecting Mitochondria, Gene Expression, and Oxidative Stress Response

Cited by 5 publications

References 92 publications

Calmodulin‐mediated events during the life cycle of the amoebozoan Dictyostelium discoideum

Calmodulin‐mediated events during the life cycle of the amoebozoan Dictyostelium discoideum

Calmodulin and Calmodulin Binding Proteins in Dictyostelium: A Primer

From biosynthesis and beyond—Loss or overexpression of the cytokinin synthesis gene, iptA, alters cytokinesis and mitochondrial and amino acid metabolism in Dictyostelium discoideum

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