ArticlePloS one2015
Behavior and Properties of Mature Lytic Granules at the Immunological Synapse of Human Cytotoxic T Lymphocytes.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 17 citations in OpenAlex.
- IFT20 regulates TFEB-dependent lytic granule biogenesis in cytotoxic T lymphocytes by orchestrating the MPR-dependent transport of granzyme B.Cell death & disease · 2025Article
- Lytic granule exocytosis at immune synapses: lessons from neuronal synapses.Frontiers in immunology · 2023Review
- Faster cytotoxicity with age: Increased perforin and granzyme levels in cytotoxic CD8Aging cell · 2022Article
- Shedding Structured Light on Molecular Immunity: The Past, Present and Future of Immune Cell Super Resolution Microscopy.Frontiers in immunology · 2021Review
- Studying the biology of cytotoxic T lymphocytes in vivo with a fluorescent granzyme B-mTFP knock-in mouse.eLife · 2020Article
- Cytotoxic Granule Exocytosis From Human Cytotoxic T Lymphocytes Is Mediated by VAMP7.Frontiers in immunology · 2019Article
- Second-Generation Histamine H1 Receptor Antagonists Suppress Delayed Rectifier KBioMed research international · 2019Article
- Single Degranulations in NK Cells Can Mediate Target Cell Killing.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Cytotoxic granule endocytosis depends on the Flower protein.The Journal of cell biology · 2018Article
- Cortical actin recovery at the immunological synapse leads to termination of lytic granule secretion in cytotoxic T lymphocytes.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Preparing the lethal hit: interplay between exo- and endocytic pathways in cytotoxic T lymphocytes.Cellular and molecular life sciences : CMLS · 2017Review
- Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Killing of virally infected cells or tumor cells by cytotoxic T lymphocytes requires targeting of lytic granules to the junction between the CTL and its target. We used whole-cell patch clamp to measure the cell capacitance at fixed intracellular [Ca2+] to study fusion of lytic granules in human CTLs. Expression of a fluorescently labeled human granzyme B construct allowed identification of lytic granule fusion using total internal reflection fluorescence microscopy. In this way capacitance steps due to lytic granule fusion were identified. Our goal was to determine the size of fusing lytic granules and to describe their behavior at the plasma membrane. On average, 5.02 ± 3.09 (mean ± s.d.) lytic granules were released per CTL. The amplitude of lytic granule fusion events was ~ 3.3 fF consistent with a diameter of about 325 nm. Fusion latency was biphasic with time constants of 15.9 and 106 seconds. The dwell time of fusing lytic granules was exponentially distributed with a mean dwell time of 28.5 seconds. Fusion ended in spite of the continued presence of granules at the immune synapse. The mobility of fusing granules at the membrane was indistinguishable from that of lytic granules which failed to fuse. While dwelling at the plasma membrane lytic granules exhibit mobility consistent with docking interspersed with short periods of greater mobility. The failure of lytic granules to fuse when visible in TIRF at the membrane may indicate that a membrane-confined reaction is rate limiting.
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