ArticleProceedings of the National Academy of Sciences of the United States of America2020
Centrioles control the capacity, but not the specificity, of cytotoxic T cell killing.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Development of the fluorescent probe CenSpark for labeling centrioles and cilia.Nature chemical biology · 2026Article
- A centrally positioned cluster of multiple centrioles in antigen-presenting cells fosters T cell activation.Nature communications · 2026Article
- Cytotoxic T lymphocytes and their dual role in modulating blood-brain barrier integrity in immune-mediated neurological pathologies.Journal of translational medicine · 2025Review
- Mechanoregulation of lymphocyte cytotoxicity.Nature reviews. Immunology · 2025Review
- Immunological synapse: structures, molecular mechanisms and therapeutic implications in disease.Signal transduction and targeted therapy · 2025Review
- Developmental and tissue-specific roles of mammalian centrosomes.The FEBS journal · 2025Review
- The Golgi complex governs natural killer cell lytic granule positioning to promote directionality in cytotoxicity.Cell reports · 2025Article
- 3D live imaging and phenotyping of CAR-T cell mediated-cytotoxicity using high-throughput Bessel oblique plane microscopy.Nature communications · 2024Article
- Lytic granule exocytosis at immune synapses: lessons from neuronal synapses.Frontiers in immunology · 2023Review
- Nanotopography modulates cytoskeletal organization and dynamics during T cell activation.Molecular biology of the cell · 2022Article
- Mechanically active integrins target lytic secretion at the immune synapse to facilitate cellular cytotoxicity.Nature communications · 2022Article
- Article
- Review
- Cytotoxic T Lymphocyte Activation Signals Modulate Cytoskeletal Dynamics and Mechanical Force Generation.Frontiers in immunology · 2022Article
- Multifaceted roles of centrosomes in development, health, and disease.Journal of molecular cell biology · 2021Review
- Signal strength controls the rate of polarization within CTLs during killing.The Journal of cell biology · 2021Article
- Teasing out function from morphology: Similarities between primary cilia and immune synapses.The Journal of cell biology · 2021Review
- Role of Actin Cytoskeleton Reorganization in Polarized Secretory Traffic at the Immunological Synapse.Frontiers in cell and developmental biology · 2021Review
- Dynamic Microtubule Arrays in Leukocytes and Their Role in Cell Migration and Immune Synapse Formation.Frontiers in cell and developmental biology · 2021Review
- Actin Dynamics at the T Cell Synapse as Revealed by Immune-Related Actinopathies.Frontiers in cell and developmental biology · 2021Review
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Authors and funding
9 authors.
Funding
Abstract
Immunological synapse formation between cytotoxic T lymphocytes (CTLs) and the target cells they aim to destroy is accompanied by reorientation of the CTL centrosome to a position beneath the synaptic membrane. Centrosome polarization is thought to enhance the potency and specificity of killing by driving lytic granule fusion at the synapse and thereby the release of perforin and granzymes toward the target cell. To test this model, we employed a genetic strategy to delete centrioles, the core structural components of the centrosome. Centriole deletion altered microtubule architecture as expected but surprisingly had no effect on lytic granule polarization and directional secretion. Nevertheless, CTLs lacking centrioles did display substantially reduced killing potential, which was associated with defects in both lytic granule biogenesis and synaptic actin remodeling. These results reveal an unexpected role for the intact centrosome in controlling the capacity but not the specificity of cytotoxic killing.
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Registered trials
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