Evidence map›Paper›PMID 39694922›Full record

ArticleCellular and molecular life sciences : CMLS2024

Required minimal protein domain of flower for synaptobrevin2 endocytosis in cytotoxic T cells.

Keerthana Ravichandran, Claudia Schirra, Katja Urbansky, Szu-Min Tu, Nadia Alawar, Stefanie Mannebach, Elmar Krause, David Stevens, C Roy D Lancaster, Veit Flockerzi and 3 more

Erratum issuedAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cellular and molecular life sciences : CMLS, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Keerthana Ravichandran *Cellular Neurophysiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), Saarland University, 66421, Homburg, Germany.ORCID http://orcid.org/0000-0002-1657-1700
Claudia Schirra *Cellular Neurophysiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), Saarland University, 66421, Homburg, Germany.ORCID http://orcid.org/0000-0001-9923-2327
Katja UrbanskyDepartment of Structural Biology, Center of Human and Molecular Biology (ZHMB), Faculty of Medicine Building 60, Saarland University, 66421, Homburg, Germany.
Szu-Min TuCellular Neurophysiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), Saarland University, 66421, Homburg, Germany.ORCID https://orcid.org/0009-0000-0217-335X
Nadia AlawarCellular Neurophysiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), Saarland University, 66421, Homburg, Germany.ORCID http://orcid.org/0000-0002-8591-2513
Stefanie MannebachExperimental and Clinical Pharmacology and Toxicology and Preclinical Center for Molecular Signaling, Saarland University, Homburg, Germany.
Elmar KrauseCellular Neurophysiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), Saarland University, 66421, Homburg, Germany.ORCID http://orcid.org/0000-0003-0891-2373
David StevensCellular Neurophysiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), Saarland University, 66421, Homburg, Germany.ORCID http://orcid.org/0000-0003-4651-1706
C Roy D LancasterDepartment of Structural Biology, Center of Human and Molecular Biology (ZHMB), Faculty of Medicine Building 60, Saarland University, 66421, Homburg, Germany.ORCID http://orcid.org/0000-0002-2814-0051
Veit FlockerziExperimental and Clinical Pharmacology and Toxicology and Preclinical Center for Molecular Signaling, Saarland University, Homburg, Germany.ORCID http://orcid.org/0000-0001-6002-6294
Jens RettigCellular Neurophysiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), Saarland University, 66421, Homburg, Germany.ORCID http://orcid.org/0000-0001-6160-3954
Hsin-Fang ChangCellular Neurophysiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), Saarland University, 66421, Homburg, Germany. Hsin-Fang.Chang@uks.eu.ORCID https://orcid.org/0000-0002-7691-4090
Ute BechererCellular Neurophysiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), Saarland University, 66421, Homburg, Germany. Ute.Becherer@uks.eu.ORCID http://orcid.org/0000-0001-6005-7517

Funding

Deutsche Forschungsgemeinschaft IRTG 1830Deutsche Forschungsgemeinschaft SFB 894 - A10Deutsche Forschungsgemeinschaft SFB 894 - A14Deutsche Forschungsgemeinschaft SFB 894 - A9Deutsche Forschungsgemeinschaft SFB 894 - P1Saarland University Medical Center HOMFORexcellent
6 · The paper itself

Abstract

Flower, a highly conserved protein, crucial for endocytosis and cellular fitness, has been implicated in cytotoxic T lymphocyte (CTL) killing efficiency through its role in cytotoxic granule (CG) endocytosis at the immune synapse (IS). This study explores the molecular cues that govern Flower-mediated CG endocytosis by analyzing uptake of Synaptobrevin2, a protein specific to CG in mouse CTL. Using immunogold electron microscopy and total internal fluorescence microscopy, we found that Flower translocates in a stimulus-dependent manner from small vesicles to the IS, thereby ensuring specificity in CG membrane protein recycling. Using confocal live-cell imaging, we assessed the ability of a range of naturally occurring mouse, human and Drosophila isoforms to rescue defective endocytosis in Flower KO CTLs. This analysis demonstrated that the N-terminal portion of the protein, encompassing amino acids 1-106 in mice, is the minimal domain necessary for Synaptobrevin2 endocytosis. Additionally, we identified two pivotal sites through site-specific mutation: a putative AP2-binding site, and a tyrosine at position 104 in mouse Flower. These findings provide insights into Flower's specific functional domain essential for CG endocytosis, which is a key process in mediating T cell serial killing required for the effective fight against cancer.

Indexed as

EndocytosisProtein DomainsT-Lymphocytes, CytotoxicVesicle-Associated Membrane Protein 2AnimalsHumansImmunological SynapsesMiceMice, Inbred C57BLMice, KnockoutVesicle-Associated Membrane Protein 2CACFD1CD8 + lymphocyteEndocytosisImmunological synapseLytic granule

Identifiers

PMID39694922
PMCPMC11655906

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.