ArticleThe Journal of biological chemistry2012
Pannexin 1, an ATP release channel, is activated by caspase cleavage of its pore-associated C-terminal autoinhibitory region.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 189 papers.
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Who cites it
189 citing papers in PubMed, 297 citations in OpenAlex.
- The NLRP3 inflammasome at the crossroads of innate immune signaling and cell death.Cellular & molecular immunology · 2026Review
- Cross-Presentation and Activation of CD8+ T Cells: The Role of Pannexin-1 in Dendritic Cells.International journal of molecular sciences · 2026Article
- Small Cell Lung Cancer Establishes a Metabolic Autocrine Mechanism Through Active Extracellular ATP Transport.Cancer science · 2026Article
- Connexin-Pannexin duality in glioblastoma.Cell and tissue research · 2026Review
- ATP increases murine neuroblastoma cell size through a PANX1- and macropinocytosis-dependent mechanism.Biology open · 2025Article
- Pannexins in the vasculature.American journal of physiology. Heart and circulatory physiology · 2025Review
- Inter-platelet communication driving thrombus formation is regulated by extracellular calpain-1 cleavage of connexin 62.Haematologica · 2025Article
- Dual role for pannexin 1 at synapses: regulating functional and morphological plasticity.The Journal of physiology · 2025Review
- Article
- The Ethanolic Extract of Polygala paniculata L. Blocks Panx1 Channels and Reduces Ischemic Brain Infarct in a Dose- and Sex-Dependent Way.Molecular neurobiology · 2025Article
- Novel Naphthyridones Targeting Pannexin 1 for Colitis Management.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Pannexin channels in inflammation and tumorigenesis.Frontiers in cell and developmental biology · 2025Review
- The impact of Panx1 on inflammation, immunity, and cancer: a comprehensive review.Frontiers in medicine · 2025Review
- The C-terminal activating domain promotes pannexin 1 channel opening.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Hyperactivation of SREBP induces pannexin-1-dependent lytic cell death.Journal of lipid research · 2024Article
- CaProceedings of the National Academy of Sciences of the United States of America · 2024Article
- The C-terminal activating domain promotes Panx1 channel opening.bioRxiv : the preprint server for biology · 2024Article
- NMDAR-mediated activation of pannexin1 channels contributes to the detonator properties of hippocampal mossy fiber synapses.iScience · 2024Article
- Cryo-EM structures of pannexin 1 and 3 reveal differences among pannexin isoforms.Nature communications · 2024Article
- The small molecule raptinal can simultaneously induce apoptosis and inhibit PANX1 activity.Cell death & disease · 2024Article
129 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Pannexin 1 (PANX1) channels mediate release of ATP, a "find-me" signal that recruits macrophages to apoptotic cells; PANX1 activation during apoptosis requires caspase-mediated cleavage of PANX1 at its C terminus, but how the C terminus inhibits basal channel activity is not understood. Here, we provide evidence suggesting that the C terminus interacts with the human PANX1 (hPANX1) pore and that cleavage-mediated channel activation requires disruption of this inhibitory interaction. Basally silent hPANX1 channels localized on the cell membrane could be activated directly by protease-mediated C-terminal cleavage, without additional apoptotic effectors. By serial deletion, we identified a C-terminal region just distal to the caspase cleavage site that is required for inhibition of hPANX1; point mutations within this small region resulted in partial activation of full-length hPANX1. Consistent with the C-terminal tail functioning as a pore blocker, we found that truncated and constitutively active hPANX1 channels could be inhibited, in trans, by the isolated hPANX1 C terminus either in cells or when applied directly as a purified peptide in inside-out patch recordings. Furthermore, using a cysteine cross-linking approach, we showed that relief of inhibition following cleavage requires dissociation of the C terminus from the channel pore. Collectively, these data suggest a mechanism of hPANX1 channel regulation whereby the intact, pore-associated C terminus inhibits the full-length hPANX1 channel and a remarkably well placed caspase cleavage site allows effective removal of key inhibitory C-terminal determinants to activate hPANX1.
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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.