ArticleScience signaling2016
Computational spatiotemporal analysis identifies WAVE2 and cofilin as joint regulators of costimulation-mediated T cell actin dynamics.
Article in Science signaling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 27 citations in OpenAlex.
- Advances in ligand-based surface engineering strategies for fine-tuning T cell mechanotransduction toward efficient immunotherapy.Biophysical journal · 2025Review
- 3D live imaging and phenotyping of CAR-T cell mediated-cytotoxicity using high-throughput Bessel oblique plane microscopy.Nature communications · 2024Article
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- Fine-grained, nonlinear registration of live cell movies reveals spatiotemporal organization of diffuse molecular processes.PLoS computational biology · 2022Article
- Synergistic phase separation of two pathways promotes integrin clustering and nascent adhesion formation.eLife · 2022Article
- The application of mechanobiotechnology for immuno-engineering and cancer immunotherapy.Frontiers in cell and developmental biology · 2022Review
- Article
- Actin Dynamics at the T Cell Synapse as Revealed by Immune-Related Actinopathies.Frontiers in cell and developmental biology · 2021Review
- PD-1 suppresses the maintenance of cell couples between cytotoxic T cells and target tumor cells within the tumor.Science signaling · 2020Article
- Article
- Evaluation of methods for generative modeling of cell and nuclear shape.Bioinformatics (Oxford, England) · 2019Article
- Origin, Organization, Dynamics, and Function of Actin and Actomyosin Networks at the T Cell Immunological Synapse.Annual review of immunology · 2019Review
- The Actin-Capping Protein Alpha-Adducin Is Required for T-Cell Costimulation.Frontiers in immunology · 2019Article
- Micropipette force probe to quantify single-cell force generation: application to T-cell activation.Molecular biology of the cell · 2017Article
- Image-based spatiotemporal causality inference for protein signaling networks.Bioinformatics (Oxford, England) · 2017Article
- PKCθ links proximal T cell and Notch signaling through localized regulation of the actin cytoskeleton.eLife · 2017Article
- Systems Imaging of the Immune Synapse.Methods in molecular biology (Clifton, N.J.) · 2017Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Fluorescence microscopy is one of the most important tools in cell biology research because it provides spatial and temporal information to investigate regulatory systems inside cells. This technique can generate data in the form of signal intensities at thousands of positions resolved inside individual live cells. However, given extensive cell-to-cell variation, these data cannot be readily assembled into three- or four-dimensional maps of protein concentration that can be compared across different cells and conditions. We have developed a method to enable comparison of imaging data from many cells and applied it to investigate actin dynamics in T cell activation. Antigen recognition in T cells by the T cell receptor (TCR) is amplified by engagement of the costimulatory receptor CD28. We imaged actin and eight core actin regulators to generate over a thousand movies of T cells under conditions in which CD28 was either engaged or blocked in the context of a strong TCR signal. Our computational analysis showed that the primary effect of costimulation blockade was to decrease recruitment of the activator of actin nucleation WAVE2 (Wiskott-Aldrich syndrome protein family verprolin-homologous protein 2) and the actin-severing protein cofilin to F-actin. Reconstitution of WAVE2 and cofilin activity restored the defect in actin signaling dynamics caused by costimulation blockade. Thus, we have developed and validated an approach to quantify protein distributions in time and space for the analysis of complex regulatory systems.
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Registered trials
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.