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- Actin cytoskeleton dynamics (1)
- D. discoideum (1)
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Self-organized patterns in the actin cytoskeleton are essential for eukaryotic cellular life. They are the building blocks of many functional structures that often operate simultaneously to facilitate, for example, nutrient uptake and movement of cells. However, identifying how qualitatively distinct actin patterns can coexist remains a challenge.
Using bifurcation theory of a mass conserved activator-inhibitor system, we uncover a generic mechanism of how different actin waves-traveling waves and excitable pulses- organize and simultaneously emerge.
Live-cell imaging experiments indeed reveal that narrow, planar, and fast-moving excitable pulses may coexist with ring-shaped macropinocytic actin waves in the cortex of motile amoeboid cells.
A theory for diffusivity estimation for spatially extended activator-inhibitor dynamics modeling the evolution of intracellular signaling networks is developed in the mathematical framework of stochastic reaction-diffusion systems. In order to account for model uncertainties, we extend the results for parameter estimation for semilinear stochastic partial differential equations, as developed in Pasemann and Stannat (Electron J Stat 14(1):547-579, 2020), to the problem of joint estimation of diffusivity and parametrized reaction terms. Our theoretical findings are applied to the estimation of effective diffusivity of signaling components contributing to intracellular dynamics of the actin cytoskeleton in the model organism Dictyostelium discoideum.
The motility of adherent eukaryotic cells is driven by the dynamics of the actin cytoskeleton. Despite the common force-generating actin machinery, different cell types often show diverse modes of locomotion that differ in their shape dynamics, speed, and persistence of motion. Recently, experiments in Dictyostelium discoideum have revealed that different motility modes can be induced in this model organism, depending on genetic modifications, developmental conditions, and synthetic changes of intracellular signaling. Here, we report experimental evidence that in a mutated D. discoideum cell line with increased Ras activity, switches between two distinct migratory modes, the amoeboid and fan-shaped type of locomotion, can even spontaneously occur within the same cell. We observed and characterized repeated and reversible switchings between the two modes of locomotion, suggesting that they are distinct behavioral traits that coexist within the same cell. We adapted an established phenomenological motility model that combines a reaction-diffusion system for the intracellular dynamics with a dynamic phase field to account for our experimental findings.
During development in human erythrocytes, the malaria parasite Plasmodium falciparum internalizes a large part of the cellular content of the host cell. The internalized cytosol, consisting largely of hemoglobin, is transported to the parasite’s food vacuole where it is degraded, providing nutrients and space for growth. This host cell cytosol uptake (HCCU) is crucial for parasite survival but the parasite proteins mediating this process remain obscure. Here, we identify P. falciparum VPS45 as an essential factor in HCCU. Conditional inactivation of PfVPS45 led to an accumulation of host cell cytosol-filled vesicles within the parasite and inhibited the delivery of hemoglobin to the parasite's digestive vacuole, resulting in arrested parasite growth. A proportion of these HCCU vesicle intermediates was positive for phosphatidylinositol 3-phosphate, suggesting endosomal characteristics. Thus PfVPS45 provides insight into the elusive machinery of the ingestion pathway in a parasite that contains an endolysosomal system heavily repurposed for protein secretion.