ArticleBiophysical journal2004
Two complementary, local excitation, global inhibition mechanisms acting in parallel can explain the chemoattractant-induced regulation of PI(3,4,5)P3 response in dictyostelium cells.
Article in Biophysical journal, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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78 citing papers in PubMed, 155 citations in OpenAlex.
- Emergent eukaryotic directional sensing via receptor degradation and diffusion.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A systems approach to investigate GPCR-mediated Ras signaling network in chemoattractant sensing.Molecular biology of the cell · 2022Article
- Three-dimensional stochastic simulation of chemoattractant-mediated excitability in cells.PLoS computational biology · 2021Article
- Effects of spatial confinement on migratory properties of Dictyostelium discoideum cells.Communicative & integrative biology · 2021Article
- Tools for computational analysis of moving boundary problems in cellular mechanobiology.Wiley interdisciplinary reviews. Systems biology and medicine · 2020Review
- Membrane Tension Can Enhance Adaptation to Maintain Polarity of Migrating Cells.Biophysical journal · 2020Article
- Spatial gradient sensing and chemotaxis via excitability in Dictyostelium discoideum.Physical review. E · 2020Article
- Simple Rho GTPase Dynamics Generate a Complex Regulatory Landscape Associated with Cell Shape.Biophysical journal · 2020Article
- A computational model for how cells choose temporal or spatial sensing during chemotaxis.PLoS computational biology · 2018Article
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- Two independent but synchronized Gβγ subunit-controlled pathways are essential for trailing-edge retraction during macrophage migration.The Journal of biological chemistry · 2017Article
- Mechanisms of Cell Polarization.Current opinion in systems biology · 2017Article
- Enhanced Directional Migration of Cancer Stem Cells in 3D Aligned Collagen Matrices.Biophysical journal · 2017Article
- Exploring the inhibitory effect of membrane tension on cell polarization.PLoS computational biology · 2017Article
- Multi-phasic bi-directional chemotactic responses of the growth cone.Scientific reports · 2016Article
- A mathematical model of GTPase pattern formation during single-cell wound repair.Interface focus · 2016Review
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- Systems Biology of Immunomodulation for Post-Stroke Neuroplasticity: Multimodal Implications of Pharmacotherapy and Neurorehabilitation.Frontiers in neurology · 2016Article
- Distinct predictive performance of Rac1 and Cdc42 in cell migration.Scientific reports · 2015Article
18 more citing papers are in PubMed but not listed here.
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5 authors at 1 institution in 1 country.
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Abstract
Chemotaxing cells, such as Dictyostelium and mammalian neutrophils, sense shallow chemoattractant gradients and respond with highly polarized changes in cell morphology and motility. Uniform chemoattractant stimulation induces the transient translocations of several downstream signaling components, including phosphoinositide 3-kinase (PI3K), tensin homology protein (PTEN), and phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3). In contrast, static spatial chemoattractant gradients elicit the persistent, amplified localization of these molecules. We have proposed a model in which the response to chemoattractant is regulated by a balance of a local excitation and a global inhibition, both of which are controlled by receptor occupancy. This model can account for both the transient and spatial responses to chemoattractants, but alone does not amplify the external gradient. In this article, we develop a model in which parallel local excitation, global inhibition mechanisms control the membrane binding of PI3K and PTEN. Together, the action of these enzymes induces an amplified PI(3,4,5)P3 response that agrees quantitatively with experimentally obtained plekstrin homology-green fluorescent protein distributions in latrunculin-treated cells. We compare the model's performance with that of several mutants in which one or both of the enzymes are disrupted. The model accounts for the observed response to multiple, simultaneous chemoattractant cues and can recreate the cellular response to combinations of temporal and spatial stimuli. Finally, we use the model to predict the response of a cell where only a fraction is stimulated by a saturating dose of chemoattractant.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.