ArticleThe Journal of cell biology2001
Defective granule exocytosis in Rab27a-deficient lymphocytes from Ashen mice.
Article in The Journal of cell biology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers.
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Who cites it
100 citing papers in PubMed, 241 citations in OpenAlex.
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- TBC1D30 regulates proinsulin and insulin secretion and is the target of a genomic association signal for proinsulin.Diabetologia · 2025Article
- Case Report: Late-onset primary hemophagocytic lymphohistiocytosis leading to the diagnosis of Griscelli syndrome type 2 in a young woman with phenotypically inapparent partial albinism.Frontiers in immunology · 2025Article
- Extracellular Vesicles in Pathophysiology: A Prudent Target That Requires Careful Consideration.Cells · 2024Review
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- MADD regulates natural killer cell degranulation through Rab27a activation.Journal of cell science · 2024Article
- Correction of Griscelli Syndrome Type 2 causing mutations in theTurkish journal of biology = Turk biyoloji dergisi · 2024Article
- Cytotoxic T lymphocytes require transcription for infiltration but not target cell lysis.EMBO reports · 2023Article
- Novel RAB27A Variant Associated with Late-Onset Hemophagocytic Lymphohistiocytosis Alters Effector Protein Binding.Journal of clinical immunology · 2022Article
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- Deletion in chromosome 6 spanning alpha-synuclein and multimerin1 loci in the Rab27a/b double knockout mouse.Scientific reports · 2022Article
- Locked and Loaded: Mechanisms Regulating Natural Killer Cell Lytic Granule Biogenesis and Release.Frontiers in immunology · 2022Review
- In vivo Roles of Rab27 and Its Effectors in Exocytosis.Cell structure and function · 2021Review
- Review
- Development, characterization, and hematopoietic differentiation of Griscelli syndrome type 2 induced pluripotent stem cells.Stem cell research & therapy · 2021Article
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- Designed improvement to T-cell immunotherapy by multidimensional single cell profiling.Journal for immunotherapy of cancer · 2021Article
- Inhibition of Rab27a and Rab27b Has Opposite Effects on the Regulation of Hair Cycle and Hair Growth.International journal of molecular sciences · 2020Article
- Exophilin-5 regulates allergic airway inflammation by controlling IL-33-mediated Th2 responses.The Journal of clinical investigation · 2020Article
40 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Because mutations in Rab27a have been linked to immune defects in humans, we have examined cytotoxic lymphocyte function in ashen mice, which contain a splicing mutation in Rab27a. Ashen cytotoxic T lymphocytes (CTLs) showed a >90% reduction in lytic activity on Fas-negative target cells compared with control C3H CTLs, and ashen natural killer cell activity was likewise diminished. Although their granule-mediated cytotoxicity pathway is profoundly defective, ashen CTLs displayed a normal FasL-Fas cytotoxicity pathway. The CD4/8 phenotype of ashen T cells and their proliferative responses were similar to controls. Ashen CTLs had normal levels of perforin and granzymes A and B and normal-appearing perforin-positive granules, which polarized upon interaction of the CTLs with anti-CD3-coated beads. However, rapid anti-CD3-induced granule secretion was drastically defective in both CD8(+) and CD4(+) T cells from ashen mice. This defect in exocytosis was not observed in the constitutive pathway, as T cell receptor-stimulated interferon-gamma secretion was normal. Based on these results and our demonstration that Rab27a colocalizes with granzyme B-positive granules and is undetectable in ashen CTLs, we conclude that Rab27a is required for a late step in granule exocytosis, compatible with current models of Rab protein function in vesicle docking and fusion.
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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.