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 Molecular networking in the neuronal ceroid lipofuscinoses: insights from mammalian models and the social amoeba Dictyostelium discoideum

2020 ◽  
Vol 27 (1) ◽  
Author(s):  
Robert J. Huber
Keyword(s):  
Dictyostelium Discoideum ◽  
Mammalian Cells ◽  
Batten Disease ◽  
Neuronal Ceroid Lipofuscinoses ◽  
Common Disease ◽  
Cellular Mechanisms ◽  
Molecular Networking ◽  
Social Amoeba ◽  
Cellular Models ◽  
The Social

Abstract The neuronal ceroid lipofuscinoses (NCLs), commonly known as Batten disease, belong to a family of neurological disorders that cause blindness, seizures, loss of motor function and cognitive ability, and premature death. There are 13 different subtypes of NCL that are associated with mutations in 13 genetically distinct genes (CLN1-CLN8, CLN10-CLN14). Similar clinical and pathological profiles of the different NCL subtypes suggest that common disease mechanisms may be involved. As a result, there have been many efforts to determine how NCL proteins are connected at the cellular level. A main driving force for NCL research has been the utilization of mammalian and non-mammalian cellular models to study the mechanisms underlying the disease. One non-mammalian model that has provided significant insight into NCL protein function is the social amoeba Dictyostelium discoideum. Accumulated data from Dictyostelium and mammalian cells show that NCL proteins display similar localizations, have common binding partners, and regulate the expression and activities of one another. In addition, genetic models of NCL display similar phenotypes. This review integrates findings from Dictyostelium and mammalian models of NCL to highlight our understanding of the molecular networking of NCL proteins. The goal here is to help set the stage for future work to reveal the cellular mechanisms underlying the NCLs.

scholarly journals Bio-electrospraying and aerodynamically assisted bio-jetting the model eukaryotic Dictyostelium discoideum : assessing stress and developmental competency post treatment

2011 ◽  
Vol 8 (61) ◽  
pp. 1185-1191 ◽  
Author(s):  
Nicholl K. Pakes ◽  
Suwan N. Jayasinghe ◽  
Robin S. B. Williams
Keyword(s):  
Stress Response ◽  
Dictyostelium Discoideum ◽  
Immune Cell ◽  
Single Cells ◽  
Model Organism ◽  
Cell Types ◽  
Cell Development ◽  
Biomedical Model ◽  
Wide Range ◽  
Generalized Stress Response

Bio-electrospraying (BES) and aerodynamically assisted bio-jetting (AABJ) have recently been established as important novel biospray technologies for directly manipulating living cells. To elucidate their potential in medical and clinical sciences, these bio-aerosol techniques have been subjected to increasingly rigorous investigations. In parallel to these studies, we wish to introduce these unique biotechnologies for use in the basic biological sciences, for handling a wide range of cell types and systems, thus increasing the range and the scope of these techniques for modern research. Here, the authors present the analysis of the new use of these biospray techniques for the direct handling of the simple eukaryotic biomedical model organism Dictyostelium discoideum . These cells are widely used as a model for immune cell chemotaxis and as a simple model for development. We demonstrate that AABJ of these cells did not cause cell stress, as defined by the stress-gene induction, nor affect cell development. Furthermore, although BES induced the increased expression of one stress-related gene ( gapA ), this was not a generalized stress response nor did it affect cell development. These data suggest that these biospray techniques can be used to directly manipulate single cells of this biomedical model without inducing a generalized stress response or perturbing later development.

scholarly journals Modelling of Neuronal Ceroid Lipofuscinosis Type 2 in Dictyostelium discoideum Suggests That Cytopathological Outcomes Result from Altered TOR Signalling

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 469 ◽  
Author(s):  
Paige K. Smith ◽  
Melodi G. Sen ◽  
Paul R. Fisher ◽  
Sarah J. Annesley
Keyword(s):  
Dictyostelium Discoideum ◽  
Neuronal Ceroid Lipofuscinosis ◽  
Clinical Manifestations ◽  
Batten Disease ◽  
Neuronal Ceroid Lipofuscinoses ◽  
Antisense Inhibition ◽  
Phenotypic Characterisation ◽  
Cellular Slime ◽  
Multiple Cell

The neuronal ceroid lipofuscinoses comprise a group of neurodegenerative disorders with similar clinical manifestations whose precise mechanisms of disease are presently unknown. We created multiple cell lines each with different levels of reduction of expression of the gene coding for the type 2 variant of the disease, Tripeptidyl peptidase (Tpp1), in the cellular slime mould Dictyostelium discoideum. Knocking down Tpp1 in Dictyostelium resulted in the accumulation of autofluorescent material, a characteristic trait of Batten disease. Phenotypic characterisation of the mutants revealed phenotypic deficiencies in growth and development, whilst endocytic uptake of nutrients was enhanced. Furthermore, the severity of the phenotypes correlated with the expression levels of Tpp1. We propose that the phenotypic defects are due to altered Target of Rapamycin (TOR) signalling. We show that treatment of wild type Dictyostelium cells with rapamycin (a specific TOR complex inhibitor) or antisense inhibition of expression of Rheb (Ras homologue enriched in the brain) (an upstream TOR complex activator) phenocopied the Tpp1 mutants. We also show that overexpression of Rheb rescued the defects caused by antisense inhibition of Tpp1. These results suggest that the TOR signalling pathway is responsible for the cytopathological outcomes in the Dictyostelium Tpp1 model of Batten disease.

scholarly journals Dictyostelium discoideum and autophagy – a perfect pair

2019 ◽  
Vol 63 (8-9-10) ◽  
pp. 485-495 ◽  
Author(s):  
Sarah Fischer ◽  
Ludwig Eichinger
Keyword(s):  
Dictyostelium Discoideum ◽  
Membrane Vesicles ◽  
Model Organisms ◽  
Protein Assemblies ◽  
Large Protein ◽  
Complex Dynamic ◽  
The Social ◽  
Wide Range ◽  
Molecular Machinery ◽  
Chaperone Mediated Autophagy

Autophagy is subdivided into chaperone-mediated autophagy, microautophagy and macroautophagy and is a highly conserved intracellular degradative pathway. It is crucial for cellular homeostasis and also serves as a response to different stresses. Here we focus on macroautophagy, which targets damaged organelles and large protein assemblies, as well as pathogenic intracellular microbes for destruction. During this process, cytosolic material becomes enclosed in newly generated double-membrane vesicles, the so-called autophagosomes. Upon maturation, the autophagosome fuses with the lysosome for degradation of the cargo. The basic molecular machinery that controls macroautophagy works in a sequential order and consists of the ATG1 complex, the PtdIns3K complex, the membrane delivery system, two ubiquitin-like conjugation systems, and autophagy adaptors and receptors. Since the different stages of macroautophagy from initiation to final degradation of cargo are tightly regulated and highly conserved across eukaryotes, simple model organisms in combination with a wide range of techniques contributed significantly to advance our understanding of this complex dynamic process. Here, we present the social amoeba Dictyostelium discoideum as an advantageous and relevant experimental model system for the analysis of macroautophagy.

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 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 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 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 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.

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