Dictyostelium discoideum: A Model System for Neurological Disorders

Storey, Claire; Williams, Robin S. B.; Fisher, Paul R.; Annesley, Sarah J.

doi:10.3390/cells11030463

Cited by 8 publications

(3 citation statements)

References 196 publications

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“…In both organisms, the Phosphatidylinositol (3,4,5)-trisphosphate (PIP3) molecule acts as a pivotal player in orchestrating cellular responses, serving as a key regulator for directional migration and cell polarization (Arai et al, 2010; Posor et al, 2022). The self-organized patterns of PIP3 waves observed in Dictyostelium cells have drawn attention for their relevance to similar processes in mammalian cells, and have been used as an alternative experimental model system for many human diseases (Williams, 2010; Mathavarajah et al, 2017; Haver and Scaglione, 2021; Storey et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

Self-organization of PIP3 signaling is controlled by the confinement, topology, and curvature of the cell membrane

Erisis,

Hörning

2024

Preprint

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PIP3 is a signaling lipid on the plasma membrane that plays a fundamental role in cell signaling with a strong impact on cell physiology and diseases. It is responsible for the protruding edge formation, cell polarization, macropinocytosis and other membrane remodeling dynamics in cells. It has been shown that the membrane confinement and curvature affects the wave formation of PIP3 and F-actin. But even in the absence of F-actin, a complex self-organization of the spatiotemporal PIP3 waves is observed. In recent findings, we have shown that these waves can be guided and pinned on strongly bended Dictyostelium membranes caused by molecular crowding and curvature limited diffusion. Based on these experimental findings, we investigate the spatiotemporal PIP3 wave dynamics on realist 3D cell-like membranes to explore the effect of curvature limited diffusion, as observed experimentally. We use an established stochastic reaction-diffusion model with enzymatic Michaelis-Menten type reactions that mimics the dynamics of Dictyostelium cells. As these cells mimic the 3D shape and size observed experimentally, we found that the PIP3 wave directionality can be explained by a Hopf-like and a reverse periodic-doubling bifurcation for uniform diffusion and curvature limited diffusion properties. Finally, we compare the results with recent experimental findings and discuss the discrepancy between the biological and numerical results.

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Section: Introductionmentioning

confidence: 99%

Self-organization of PIP3 signaling is controlled by the confinement, topology, and curvature of the cell membrane

Erisis,

Hörning

2024

Preprint

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“…For many years Dictyostelium has been used to explore basic principles in cell and developmental biology, and more recently it has emerged as a valuable biomedical model system for studying several human diseases [ 13 , 14 ]. Dictyostelium cells are intrinsically motile and serve as an excellent model to analyze cell motility and host defense [ 13 , 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Centrosome Positioning in Migrating Dictyostelium Cells

Ishikawa-Ankerhold

Kroll²,

Heuvel

et al. 2022

Cells

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Directional cell migration and the establishment of polarity play an important role in development, wound healing, and host cell defense. While actin polymerization provides the driving force at the cell front, the microtubule network assumes a regulatory function, in coordinating front protrusion and rear retraction. By using Dictyostelium discoideum cells as a model for amoeboid movement in different 2D and 3D environments, the position of the centrosome relative to the nucleus was analyzed using live-cell microscopy. Our results showed that the centrosome was preferentially located rearward of the nucleus under all conditions tested for directed migration, while the nucleus was oriented toward the expanding front. When cells are hindered from straight movement by obstacles, the centrosome is displaced temporarily from its rearward location to the side of the nucleus, but is reoriented within seconds. This relocalization is supported by the presence of intact microtubules and their contact with the cortex. The data suggest that the centrosome is responsible for coordinating microtubules with respect to the nucleus. In summary, we have analyzed the orientation of the centrosome during different modes of migration in an amoeboid model and present evidence that the basic principles of centrosome positioning and movement are conserved between Dictyostelium and human leukocytes.

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“…Simple eukaryotes are powerful tools that are widely used to identify novel components of cellular processes and are known to be useful in genetic screening. The social amoeba Dictyostelium discoideum is a simple and valuable biomedical model that is recognised by the National Institute of Health for studying the functions of proteins associated with human diseases 1 – 3 . Moreover, because of its unique developmental life cycle and capacity to produce specific secondary metabolites and signalling molecules, Dictyostelium can also be used to study multicellular features, such as cell–cell communication and cell migration, and the production of chemical compounds and substances, such as aromatic polyketides 4 – 8 .…”

Section: Introductionmentioning

confidence: 99%

CRISPR/Cas9-based genome-wide screening of Dictyostelium

Ogasawara

Watanabe

Adachi

et al. 2022

Sci Rep

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Genome-wide screening is powerful method used to identify genes and pathways associated with a phenotype of interest. The simple eukaryote Dictyostelium discoideum has a unique life cycle and is often used as a crucial research model for a wide range of biological processes and rare metabolites. To address the inadequacies of conventional genetic screening approaches, we developed a highly efficient CRISPR/Cas9-based genome-wide screening system for Dictyostelium. A genome-wide library of 27,405 gRNAs and a kinase library of 4,582 gRNAs were compiled and mutant pools were generated. The resulting mutants were screened for defects in cell growth and more than 10 candidate genes were identified. Six of these were validated and five recreated mutants presented with growth abnormalities. Finally, the genes implicated in developmental defects were screened to identify the unknown genes associated with a phenotype of interest. These findings demonstrate the potential of the CRISPR/Cas9 system as an efficient genome-wide screening method.

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Dictyostelium discoideum: A Model System for Neurological Disorders

Cited by 8 publications

References 196 publications

Self-organization of PIP3 signaling is controlled by the confinement, topology, and curvature of the cell membrane

Self-organization of PIP3 signaling is controlled by the confinement, topology, and curvature of the cell membrane

Centrosome Positioning in Migrating Dictyostelium Cells

CRISPR/Cas9-based genome-wide screening of Dictyostelium

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