ArticleEMBO reports2019
Pannexin-1 limits the production of proinflammatory cytokines during necroptosis.
Article in EMBO reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Multi-ancestry genome-wide association analyses provide insights into the genetic basis of Hashimoto's thyroiditis.Nature genetics · 2026Pooled it
- RIP kinase inhibition with Necrostatin-1 improves human marginal mass islet graft survival and function for the management of type 1 diabetes.Cell death & disease · 2026Article
- Proximal tubule pannexin 1 contributes to mitochondrial dysfunction and cell death during acute kidney injury.American journal of physiology. Renal physiology · 2025Article
- The impact of Panx1 on inflammation, immunity, and cancer: a comprehensive review.Frontiers in medicine · 2025Review
- Cryo-EM structures of pannexin 1 and 3 reveal differences among pannexin isoforms.Nature communications · 2024Article
- Global pannexin 1 deletion increases tumor-infiltrating lymphocytes in the BRAF/Pten mouse melanoma model.Molecular oncology · 2024Article
- The small molecule raptinal can simultaneously induce apoptosis and inhibit PANX1 activity.Cell death & disease · 2024Article
- TNFα modulates PANX1 activation to promote ATP release and enhance P2RX7-mediated antitumor immune responses after chemotherapy in colorectal cancer.Cell death & disease · 2024Article
- The centrosomal protein 131 participates in the regulation of mitochondrial apoptosis.Communications biology · 2023Article
- The Many Faces of MLKL, the Executor of Necroptosis.International journal of molecular sciences · 2023Review
- Expression of Connexins 37, 40 and 45, Pannexin 1 and Vimentin in Laryngeal Squamous Cell Carcinomas.Genes · 2023Article
- Inhibition of the pseudokinase MLKL alters extracellular vesicle release and reduces tumor growth in glioblastoma.iScience · 2022Article
- Necroptosis is associated with Rab27-independent expulsion of extracellular vesicles containing RIPK3 and MLKL.Journal of extracellular vesicles · 2022Article
- Pannexin1 channels-a potential therapeutic target in inflammation.Frontiers in cell and developmental biology · 2022Review
- Diversity of cell death signaling pathways in macrophages upon infection with modified vaccinia virus Ankara (MVA).Cell death & disease · 2021Article
- RIPK3 modulates growth factor receptor expression in endothelial cells to support angiogenesis.Angiogenesis · 2021Article
- Structure of the full-length human Pannexin1 channel and insights into its role in pyroptosis.Cell discovery · 2021Article
- Pore formation in regulated cell death.The EMBO journal · 2020Review
- MLKL trafficking and accumulation at the plasma membrane control the kinetics and threshold for necroptosis.Nature communications · 2020Article
- Pannexin-1 Channel Regulates ATP Release in Epilepsy.Neurochemical research · 2020Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
The activation of mixed lineage kinase-like (MLKL) by receptor-interacting protein kinase-3 (RIPK3) controls the execution of necroptosis, a regulated form of necrosis that occurs in apoptosis-deficient conditions. Active oligomerized MLKL triggers the exposure of phosphatidylserine residues on the cell surface and disrupts the plasma membrane integrity by forming lytic pores. MLKL also governs endosomal trafficking and biogenesis of small extracellular vesicles as well as the production of proinflammatory cytokines during the early steps of necroptosis; however, the molecular basis continues to be elucidated. Here, we find that MLKL oligomers activate Pannexin-1 (PANX1) channels, concomitantly to the loss of phosphatidylserine asymmetry. This plasma membrane "leakiness" requires the small GTPase RAB27A and RAB27B isoforms, which regulate intracellular vesicle trafficking, docking, and fusion with the plasma membrane. Although cells in which PANX1 is silenced or inhibited normally undergo necroptotic death, they display enhanced production of cytokines such as interleukin-8, indicating that PANX1 may tamper with inflammation. These data identify a novel signaling nexus between MLKL, RAB27, and PANX1 and propose ways to interfere with inflammation associated with necroptosis.
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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.