Receptor-induced transient responses in cells with oscillatory actin dynamics

Negrete, José; Pumir, Alain; Westendorf, Christian; Tarantola, Marco; Bodenschatz, Eberhard; Beta, Carsten

doi:10.1103/physrevresearch.2.013239

Cited by 2 publications

(1 citation statement)

References 45 publications

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“…In motile D. discoideum cells, actin and associated signaling proteins spontaneously form traveling waves at the ventral cell border [32]. Analyzing these patterns, as well as patterns induced by external stimuli, can facilitate the understanding of complex signaling networks and form the basis for the development of advanced theoretical models [33,34]. In this study, we show that active Rac1 exhibits a variety of dynamic behaviors in D. discoideum cell plasma membrane.…”

Section: Introductionmentioning

confidence: 70%

Oscillatory dynamics of Rac1 activity inDictyostelium discoideumamoebae

Šoštar,

Marinović,

Filić

et al. 2024

Preprint

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Small GTPases of the Rho family play a central role in the regulation of cell motility by controlling the remodeling of the actin cytoskeleton. In the amoeboid cells of Dictyostelium discoideum, the active form of the Rho GTPase Rac1 regulates actin polymerases at the leading edge and actin filament bundling proteins at the posterior cortex of polarized cells. However, constitutive Rac1 dynamics in D. discoideum have not yet been systematically investigated. Therefore, we monitored the spatiotemporal dynamics of Rac1 activity in vegetative amoebae using a specific fluorescent probe. We observed that plasma membrane domains enriched in active Rac1 not only exhibited stable polarization, but also showed rotations and oscillations. To simulate the observed dynamics, we developed a mass-conserving reaction-diffusion model based on the circulation of Rac1 between the membrane and the cytoplasm in conjunction with its activation by GEFs, deactivation by GAPs and interaction with the Rac1 effector DGAP1. Our theoretical model accurately reproduced the experimentally observed dynamic patterns, including the predominant anti-correlation between active Rac1 and DGAP1. Significantly, the model predicted a new colocalization regime of these two proteins in polarized cells, which we confirmed experimentally. In summary, our results improve the understanding of Rac1 dynamics and reveal how the occurrence and transitions between different regimes depend on biochemical reaction rates, protein levels and cell size. This study not only expands our knowledge of the behavior of small GTPases in D. discoideum amoebae, but also provides a simple modeling framework that can be adapted to study similar dynamics in other cell types.

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Section: Introductionmentioning

confidence: 70%

Oscillatory dynamics of Rac1 activity inDictyostelium discoideumamoebae

Šoštar,

Marinović,

Filić

et al. 2024

Preprint

View full text Add to dashboard Cite

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Transient frequency preference responses in cell signaling systems

Szischik,

Reves Szemere,

Balderrama

et al. 2024

npj Syst Biol Appl

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Ligand–receptor systems, covalent modification cycles, and transcriptional networks are the fundamental components of cell signaling and gene expression systems. While their behavior in reaching a steady-state regime under step-like stimulation is well understood, their response under repetitive stimulation, particularly at early time stages is poorly characterized. Yet, early-stage responses to external inputs are arguably as informative as late-stage ones. In simple systems, a periodic stimulation elicits an initial transient response, followed by periodic behavior. Transient responses are relevant when the stimulation has a limited time span, or when the stimulated component’s timescale is slow as compared to the timescales of the downstream processes, in which case the latter processes may be capturing only those transients. In this study, we analyze the frequency response of simple motifs at different time stages. We use dose-conserved pulsatile input signals and consider different metrics versus frequency curves. We show that in ligand–receptor systems, there is a frequency preference response in some specific metrics during the transient stages, which is not present in the periodic regime. We suggest this is a general system-level mechanism that cells may use to filter input signals that have consequences for higher order circuits. In addition, we evaluate how the described behavior in isolated motifs is reflected in similar types of responses in cascades and pathways of which they are a part. Our studies suggest that transient frequency preferences are important dynamic features of cell signaling and gene expression systems, which have been overlooked.

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Receptor-induced transient responses in cells with oscillatory actin dynamics

Cited by 2 publications

References 45 publications

Oscillatory dynamics of Rac1 activity inDictyostelium discoideumamoebae

Oscillatory dynamics of Rac1 activity inDictyostelium discoideumamoebae

Transient frequency preference responses in cell signaling systems

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