ArticleThe Journal of cell biology2020
The septin cytoskeleton regulates natural killer cell lytic granule release.
Article in The Journal of cell biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 13 citations in OpenAlex.
- Targeting leukemic stem cell biomechanics suppresses stemness and enhances NK cell-mediated immunotherapy.Nature communications · 2025Article
- Loss of HD-PTP function results in lipodystrophy, defective cellular signaling and altered lipid homeostasis.Journal of cell science · 2024Article
- Venetoclax acts as an immunometabolic modulator to potentiate adoptive NK cell immunotherapy against leukemia.Cell reports. Medicine · 2024Article
- MADD regulates natural killer cell degranulation through Rab27a activation.Journal of cell science · 2024Article
- Microfluidic Organoid Cultures Derived from Pancreatic Cancer Biopsies for Personalized Testing of Chemotherapy and Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Septins as membrane influencers: direct play or in association with other cytoskeleton partners.Frontiers in cell and developmental biology · 2023Review
- Locked and Loaded: Mechanisms Regulating Natural Killer Cell Lytic Granule Biogenesis and Release.Frontiers in immunology · 2022Review
- RHO GTPases: from new partners to complex immune syndromes.Nature reviews. Immunology · 2021Review
- The state of the septin cytoskeleton from assembly to function.Current opinion in cell biology · 2021Review
- Identification and Structure Prediction of Human Septin-4 as a Biomarker for Diagnosis of Asthenozoospermic Infertile Patients-Critical Finding Toward Personalized Medicine.Frontiers in medicine · 2021Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Natural killer (NK) cell-mediated killing involves the membrane fusion of preformed lytic granules. While the roles of actin and microtubules are well accepted during this process, the function of septins, another cytoskeletal component that associates with actin and microtubules, has not been investigated. Here we show that genetic depletion or pharmacologic stabilization of the septin cytoskeleton significantly inhibited NK cell cytotoxicity. Although the stabilization of septin filaments impaired conjugate formation, depletion of septin proteins had no impact on conjugate formation, lytic granule convergence, or MTOC polarization to the cytotoxic synapse (CS). Interestingly, septins copurify and accumulate near the polarized lytic granules at the CS, where they regulate lytic granule release. Mechanistically, we find that septin 7 interacts with the SNARE protein syntaxin 11 and facilitates its interaction with syntaxin binding protein 2 to promote lytic granule fusion. Altogether, our data identify a critical role for septins in regulating the release of lytic granule contents during NK cell-mediated killing.
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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.