scholarly journals Mitochondrial regulation in Dictyostelium discoideum

2018 ◽  
Author(s):  
Mehak Rafiq
Keyword(s):  
Dictyostelium Discoideum ◽  
Serine Proteases ◽  
Model Organism ◽  
Complex Life Cycle ◽  
Transcriptional Networks ◽  
Multicellular Development ◽  
Mitochondrial Regulation ◽  
Rhomboid Proteases ◽  
The Social ◽  
Membrane Bound

Proteolysis is increasingly documented as a method of regulation of mitochondrial function. Our studies of rhomboidfamily proteins’ roles in organelles show that this is also the case in the social amoeba Dictyostelium discoideum, in which four of these membrane-bound, evolutionarily ubiquitous, serine proteases are found. Rhomboid proteases act on disparate substrates in different organisms so far studied, but their mode of action is conserved: their location in the membrane means that their membrane-tethered substrates can act in signalling upon release, or be activated, by rhomboid-mediated cleavage. Among eukaryotic rhomboids is the mitochondrial protease ‘PARL’, which ensures the maintenance of the structural and functional integrity of mitochondria and plastids, but we have found that other Dictyostelium rhomboids also affect the organelle. Studying the development and behaviour of Dictyostelium, a microbial model organism with a complex life cycle that includes uni- and multicellular stages, allowed investigation of the role of rhomboids in unicellular vegetative growth, multicellular development and sporulation, phagocytosis, and response to the environment. We found that two rhomboid-null mutants gave rise to changes in development, rhmA altering the response to chemoattractants and demonstrating decreased motility in general, whereas rhmB null cells had slower growth rates with decreased response to folic acid. RhmA, although located in the contractile vacuole, affects the ultrastructure of mitochondria, and RhmB-GFP fusions protein was localised to the mitochondrion. qPCR analysis revealed RhmA and RhmB transcript levels peaking during the multicellular growth phase and transcriptional networks suggest the Dictyostelium rhmA is regulated along with the orthologues of Saccharomyces cerevisiae mitochondrial rhomboid substrates.

scholarly journals Mitochondrial regulation in Dictyostelium discoideum

2018 ◽  
Author(s):  
Mehak Rafiq ◽  
Elinor Thompson
Keyword(s):  
Dictyostelium Discoideum ◽  
Serine Proteases ◽  
Model Organism ◽  
Complex Life Cycle ◽  
Transcriptional Networks ◽  
Multicellular Development ◽  
Mitochondrial Regulation ◽  
Rhomboid Proteases ◽  
The Social ◽  
Membrane Bound

Proteolysis is increasingly documented as a method of regulation of mitochondrial function. Our studies of rhomboidfamily proteins’ roles in organelles show that this is also the case in the social amoeba Dictyostelium discoideum, in which four of these membrane-bound, evolutionarily ubiquitous, serine proteases are found. Rhomboid proteases act on disparate substrates in different organisms so far studied, but their mode of action is conserved: their location in the membrane means that their membrane-tethered substrates can act in signalling upon release, or be activated, by rhomboid-mediated cleavage. Among eukaryotic rhomboids is the mitochondrial protease ‘PARL’, which ensures the maintenance of the structural and functional integrity of mitochondria and plastids, but we have found that other Dictyostelium rhomboids also affect the organelle. Studying the development and behaviour of Dictyostelium, a microbial model organism with a complex life cycle that includes uni- and multicellular stages, allowed investigation of the role of rhomboids in unicellular vegetative growth, multicellular development and sporulation, phagocytosis, and response to the environment. We found that two rhomboid-null mutants gave rise to changes in development, rhmA altering the response to chemoattractants and demonstrating decreased motility in general, whereas rhmB null cells had slower growth rates with decreased response to folic acid. RhmA, although located in the contractile vacuole, affects the ultrastructure of mitochondria, and RhmB-GFP fusions protein was localised to the mitochondrion. qPCR analysis revealed RhmA and RhmB transcript levels peaking during the multicellular growth phase and transcriptional networks suggest the Dictyostelium rhmA is regulated along with the orthologues of Saccharomyces cerevisiae mitochondrial rhomboid substrates.

scholarly journals Recent Insights into NCL Protein Function Using the Model Organism Dictyostelium discoideum

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 115 ◽  
Author(s):  
Meagan McLaren ◽  
Sabateeshan Mathavarajah ◽  
Robert Huber
Keyword(s):  
Dictyostelium Discoideum ◽  
Neurological Disorders ◽  
Protein Function ◽  
Model Organism ◽  
Batten Disease ◽  
Neuronal Ceroid Lipofuscinoses ◽  
Biomedical Model ◽  
The Social ◽  
Wide Range ◽  
Poor Understanding

The neuronal ceroid lipofuscinoses (NCLs) are a group of devastating neurological disorders that have a global distribution and affect people of all ages. Commonly known as Batten disease, this form of neurodegeneration is linked to mutations in 13 genetically distinct genes. The precise mechanisms underlying the disease are unknown, in large part due to our poor understanding of the functions of NCL proteins. The social amoeba Dictyostelium discoideum has proven to be an exceptional model organism for studying a wide range of neurological disorders, including the NCLs. The Dictyostelium genome contains homologs of 11 of the 13 NCL genes. Its life cycle, comprised of both single-cell and multicellular phases, provides an excellent system for studying the effects of NCL gene deficiency on conserved cellular and developmental processes. In this review, we highlight recent advances in NCL research using Dictyostelium as a biomedical model.

scholarly journals Optimisation of External Factors for the Growth of Francisella novicida within Dictyostelium discoideum

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Ina Kelava ◽  
Valentina Marecic ◽  
Petra Fucak ◽  
Elena Ivek ◽  
Dominik Kolaric ◽  
...  
Keyword(s):  
Dictyostelium Discoideum ◽  
Model Organism ◽  
Optimal Growth ◽  
Intracellular Bacteria ◽  
Optimal Temperature ◽  
Francisella Novicida ◽  
Host Pathogen Interaction ◽  
The Social ◽  
Different Temperatures ◽  
Low Cytotoxicity

The amoeba Dictyostelium discoideum has been used as a model organism to study host-pathogen interaction in many intracellular bacteria. Francisella tularensis is a Gram-negative, highly infectious bacterium that causes the zoonotic disease tularemia. The bacterium is able to replicate in different phagocytic and nonphagocytic cells including mammalian, amoebae, and arthropod cells. The aim of this study was to determine the optimal temperature and infection dose in the interaction of Francisella novicida with D. discoideum in order to establish a model of Francisella infection in the social amoeba. The amoeba cells were infected with a different multiplicity of infection (5, 10, and 100) and incubated at different temperatures (22, 25, 27, 30, and 37°C). The number of intracellular bacteria within D. discoideum, as well as cytotoxicity, was determined at 2, 4, 24, 48, and 72 hours after infection. Our results showed that the optimal temperature for Francisella intracellular replication within amoeba is 30°C with the MOI of 10. We can conclude that this MOI and temperature induced the optimal growth of bacteria in Dictyostelium with low cytotoxicity.

scholarly journals A Proteomics Analysis of Calmodulin-Binding Proteins in Dictyostelium discoideum during the Transition from Unicellular Growth to Multicellular Development

2021 ◽  
Vol 22 (4) ◽  
pp. 1722
Author(s):  
William D. Kim ◽  
Shyong Q. Yap ◽  
Robert J. Huber
Keyword(s):  
Dictyostelium Discoideum ◽  
Calcium Binding ◽  
Mammalian Cells ◽  
Binding Proteins ◽  
Model Organism ◽  
Developmental Processes ◽  
Multicellular Development ◽  
Calmodulin Binding ◽  
Search Tool

Calmodulin (CaM) is an essential calcium-binding protein within eukaryotes. CaM binds to calmodulin-binding proteins (CaMBPs) and influences a variety of cellular and developmental processes. In this study, we used immunoprecipitation coupled with mass spectrometry (LC-MS/MS) to reveal over 500 putative CaM interactors in the model organism Dictyostelium discoideum. Our analysis revealed several known CaMBPs in Dictyostelium and mammalian cells (e.g., myosin, calcineurin), as well as many novel interactors (e.g., cathepsin D). Gene ontology (GO) term enrichment and Search Tool for the Retrieval of Interacting proteins (STRING) analyses linked the CaM interactors to several cellular and developmental processes in Dictyostelium including cytokinesis, gene expression, endocytosis, and metabolism. The primary localizations of the CaM interactors include the nucleus, ribosomes, vesicles, mitochondria, cytoskeleton, and extracellular space. These findings are not only consistent with previous work on CaM and CaMBPs in Dictyostelium, but they also provide new insight on their diverse cellular and developmental roles in this model organism. In total, this study provides the first in vivo catalogue of putative CaM interactors in Dictyostelium and sheds additional light on the essential roles of CaM and CaMBPs in eukaryotes.

scholarly journals Reactive/Less-cooperative individuals advance population’s synchronization: Modeling of Dictyostelium discoideum concerted signaling during aggregation phase

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0259742
Author(s):  
Zahra Eidi ◽  
Najme Khorasani ◽  
Mehdi Sadeghi
Keyword(s):  
Dictyostelium Discoideum ◽  
Life Form ◽  
Single Cells ◽  
Model Organism ◽  
Chemical Signaling ◽  
Relative Population ◽  
Social Amoeba ◽  
The Social ◽  
Chemical Waves ◽  
The Waves

Orchestrated chemical signaling of single cells sounds to be a linchpin of emerging organization and multicellular life form. The social amoeba Dictyostelium discoideum is a well-studied model organism to explore overall pictures of grouped behavior in developmental biology. The chemical waves secreted by aggregating Dictyostelium is a superb example of pattern formation. The waves are either circular or spiral in shape, according to the incremental population density of a self-aggregating community of individuals. Here, we revisit the spatiotemporal patterns that appear in an excitable medium due to synchronization of randomly firing individuals, but with a more parsimonious attitude. According to our model, a fraction of these individuals are less involved in amplifying external stimulants. Our simulations indicate that the cells enhance the system’s asymmetry and as a result, nucleate early sustainable spiral territory zones, provided that their relative population does not exceed a tolerable threshold.

scholarly journals An ancestral non-proteolytic role for presenilin proteins in multicellular development of the social amoeba Dictyostelium discoideum

2014 ◽  
Vol 127 (7) ◽  
pp. 1576-1584 ◽  
Author(s):  
M. H. R. Ludtmann ◽  
G. P. Otto ◽  
C. Schilde ◽  
Z.-H. Chen ◽  
C. Y. Allan ◽  
...  
Keyword(s):  
Dictyostelium Discoideum ◽  
Multicellular Development ◽  
Social Amoeba ◽  
The Social

scholarly journals Inhibiting Neddylation with MLN4924 Suppresses Growth and Delays Multicellular Development in Dictyostelium discoideum

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 482
Author(s):  
Robert J. Huber ◽  
William D. Kim ◽  
Sabateeshan Mathavarajah
Keyword(s):  
Dictyostelium Discoideum ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Biological Processes ◽  
Neural Precursor Cell ◽  
Post Translational Modification ◽  
Fruiting Body Formation ◽  
Multicellular Development ◽  
Cellular Processes ◽  
The Social

Neddylation is a post-translational modification that is essential for a variety of cellular processes and is linked to many human diseases including cancer, neurodegeneration, and autoimmune disorders. Neddylation involves the conjugation of the ubiquitin-like modifier neural precursor cell expressed developmentally downregulated protein 8 (NEDD8) to target proteins, and has been studied extensively in various eukaryotes including fungi, plants, and metazoans. Here, we examine the biological processes influenced by neddylation in the social amoeba, Dictyostelium discoideum, using a well-established inhibitor of neddylation, MLN4924 (pevonedistat). NEDD8, and the target of MLN4924 inhibition, NEDD8-activating enzyme E1 (NAE1), are highly conserved in D. discoideum (Nedd8 and Nae1, respectively). Treatment of D. discoideum cells with MLN4924 increased the amount of free Nedd8, suggesting that MLN4924 inhibited neddylation. During growth, MLN4924 suppressed cell proliferation and folic acid-mediated chemotaxis. During multicellular development, MLN4924 inhibited cyclic adenosine monophosphate (cAMP)-mediated chemotaxis, delayed aggregation, and suppressed fruiting body formation. Together, these findings indicate that neddylation plays an important role in regulating cellular and developmental events during the D. discoideum life cycle and that this organism can be used as a model system to better understand the essential roles of neddylation in eukaryotes, and consequently, its involvement in human disease.

scholarly journals Sex Determination in the Social Amoeba Dictyostelium discoideum

Science ◽  
2010 ◽  
Vol 330 (6010) ◽  
pp. 1533-1536 ◽  
Author(s):  
Gareth Bloomfield ◽  
Jason Skelton ◽  
Alasdair Ivens ◽  
Yoshimasa Tanaka ◽  
Robert R. Kay
Keyword(s):  
Sex Determination ◽  
Dictyostelium Discoideum ◽  
Genetic Locus ◽  
Model Organism ◽  
Mating Types ◽  
Type Locus ◽  
Social Amoeba ◽  
The Third ◽  
The Social ◽  
Social Amoebae

The genetics of sex determination remain mysterious in many organisms, including some that are otherwise well studied. Here we report the discovery and analysis of the mating-type locus of the model organism Dictyostelium discoideum. Three forms of a single genetic locus specify this species' three mating types: two versions of the locus are entirely different in sequence, and the third resembles a composite of the other two. Single, unrelated genes are sufficient to determine two of the mating types, whereas homologs of both these genes are required in the composite type. The key genes encode polypeptides that possess no recognizable similarity to established protein families. Sex determination in the social amoebae thus appears to use regulators that are unrelated to any others currently known.

scholarly journals The past, present and future of Dictyostelium as a model system

2019 ◽  
Vol 63 (8-9-10) ◽  
pp. 321-331 ◽  
Author(s):  
Salvatore Bozzaro
Keyword(s):  
Dictyostelium Discoideum ◽  
Social Evolution ◽  
Model Organism ◽  
Model Organisms ◽  
Human Genes ◽  
The Social ◽  
Microbial Infections ◽  
Technological Developments ◽  
Soil Amoeba

The social amoeba Dictyostelium discoideum has been a preferred model organism during the last 50 years, particularly for the study of cell motility and chemotaxis, phagocytosis and macropinocytosis, intercellular adhesion, pattern formation, caspase-independent cell death and more recently autophagy and social evolution. Being a soil amoeba and professional phagocyte, thus exposed to a variety of potential pathogens, D. discoideum has also proven to be a powerful genetic and cellular model for investigating host-pathogen interactions and microbial infections. The finding that the Dictyostelium genome harbours several homologs of human genes responsible for a variety of diseases has stimulated their analysis, providing new insights into the mechanism of action of the encoded proteins and in some cases into the defect underlying the disease. Recent technological developments have covered the genetic gap between mammals and non-mammalian model organisms, challenging the modelling role of the latter. Is there a future for Dictyostelium discoideum as a model organism?

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