Affinage

PANX1

Pannexin-1 · UniProt Q96RD7

Length
426 aa
Mass
48.0 kDa
Annotated
2026-04-29
100 papers in source corpus 26 papers cited in narrative 27 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PANX1 is a heptameric large-pore plasma membrane channel that releases ATP and other signaling molecules to activate purinergic receptors, thereby coupling diverse cellular stimuli to inflammatory, metabolic, and neuronal signaling pathways. Cryo-EM structural analysis shows that seven W74 residues at the extracellular entrance undergo conformational switching between a chloride-permissive constricted state and an ATP-permissive dilated state, with cation-π interactions at R75 contributing to gating (PMID:41381453); intracellular Cys346 is essential for channel regulation, as its mutation produces a constitutively leaky channel (PMID:20829356). PANX1 is activated by caspase cleavage (caspases-1, -3, -5, -8), Src-family kinase phosphorylation downstream of non-ionotropic NMDA receptors, high extracellular K⁺, and P2X7 receptor engagement, and the released ATP drives NLRP3 inflammasome assembly in macrophages, LTD at hippocampal synapses via P2X4 receptors, regulation of cerebrovascular tone through microglial P2RY12, metabolic reprogramming in cardiomyocytes, and hepatic gluconeogenesis suppression via P2Y–Akt signaling (PMID:23449592, PMID:39709529, PMID:34489419, PMID:38957990, PMID:35473933, PMID:38937853). Homozygous loss-of-function PANX1 variants (e.g., p.Arg217His) cause a multisystem disorder featuring intellectual disability, hearing loss, skeletal defects, and primary ovarian failure (PMID:27129271).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 2010 High

    Identifying the gating-critical residue Cys346 established that a single intracellular cysteine controls the open-closed transition of PANX1, providing the first molecular handle on channel regulation.

    Evidence Site-directed mutagenesis with electrophysiology in Xenopus oocytes and N2A cells

    PMID:20829356

    Open questions at the time
    • Mechanism by which Cys346 controls gating (redox sensing, disulfide bonding) was not resolved
    • No structural context for Cys346 position relative to the pore
  2. 2013 High

    Demonstrating that cortical spreading depression opens neuronal PANX1, triggering caspase-1 activation and HMGB1 release leading to trigeminovascular activation, established PANX1 as a central effector linking neuronal depolarization to sterile neuroinflammation and headache pathophysiology.

    Evidence In vivo pharmacological blockade, genetic models, HMGB1/NF-κB assays, dural mast cell readouts in mice

    PMID:23449592

    Open questions at the time
    • Identity of the upstream signal that directly opens PANX1 during CSD was not established
    • Contribution of non-neuronal PANX1 in this cascade was not dissected
  3. 2013 High

    Discovery of BB FCF as a selective PANX1 inhibitor (IC50 0.27 µM) with no effect on P2X7R provided a pharmacological tool to distinguish PANX1-specific contributions from those of the P2X7–PANX1 complex.

    Evidence Dose-response electrophysiology and dye-uptake assays comparing PANX1 and P2X7R

    PMID:23589583

    Open questions at the time
    • In vivo pharmacokinetics and off-target profiling of BB FCF were not reported
    • Mechanism of BB FCF block (pore vs. allosteric) was unknown
  4. 2013 Medium

    PANX1 interaction with actin and Arp3 in neural progenitors linked the channel to cytoskeletal remodeling, cell migration, and neurite extension, expanding its role beyond ion/ATP conductance.

    Evidence Endogenous co-immunoprecipitation, scratch wound and neurite extension assays in neural stem/progenitor cells

    PMID:23964896

    Open questions at the time
    • Reciprocal validation of the PANX1–Arp3 interaction was not shown
    • Whether the cytoskeletal role is channel-activity-dependent or structural was not resolved
  5. 2014 Medium

    Cell-type-specific phenotypes in Panx1-null skin—increased keratinocyte migration but impaired fibroblast contractility and TGF-β responsiveness—revealed that PANX1 regulates wound healing through distinct mechanisms in different dermal cell types.

    Evidence Panx1 knockout mice, scratch wound, collagen gel contraction, TGF-β stimulation, probenecid blockade

    PMID:24522432

    Open questions at the time
    • Whether the wound healing defect is ATP-release-dependent was not directly tested
    • Downstream purinergic receptor identity in fibroblasts was not established
  6. 2016 High

    Identification of the homozygous p.Arg217His loss-of-function variant causing multisystem disease (intellectual disability, hearing loss, skeletal defects, ovarian failure) established PANX1 as a Mendelian disease gene and demonstrated the essential role of ATP release channel function across multiple organ systems.

    Evidence WES, dye uptake, ATP release, electrophysiology, glycosylation analysis across multiple cell lines

    PMID:27129271

    Open questions at the time
    • Tissue-specific pathogenic mechanism for each organ system was not delineated
    • Whether residual channel activity exists in vivo was not determined
  7. 2017 High

    Genetic and pharmacological epistasis between P2X7R and PANX1 in spreading depolarization showed that the P2X7–PANX1 pore complex drives neuroinflammatory cytokine release (IL-1β, iNOS, COX-2), placing both proteins in a common inflammatory signaling axis.

    Evidence P2x7 knockout and pharmacological inhibition in FHM1 knock-in mice, electrophysiology, cytokine and CGRP quantification

    PMID:28430869

    Open questions at the time
    • Stoichiometry and physical nature of the P2X7–PANX1 interaction were not resolved
    • Whether PANX1 activation is secondary to P2X7 or occurs in parallel was debated
  8. 2019 Medium

    Mapping PANX1 apical targeting to residues 307–379 and a Y308-based sorting motif showed that polarized localization is actively sorted, and its disruption causes EMT-like phenotypes, linking channel trafficking to epithelial tissue organization.

    Evidence GFP-tagged PANX1 mutagenesis in polarized MDCK cells and spheroids, fluorescence microscopy

    PMID:31102595

    Open questions at the time
    • Adaptor proteins recognizing the Y308 motif were not identified
    • Whether apical vs. basolateral PANX1 conducts differentially was not tested
  9. 2021 High

    Demonstrating that microglial PANX1-derived purines activate P2RY12 on capillary-associated microglia to regulate brain capillary structure and vasodilation established a non-neuronal, vascular function for PANX1 purinergic signaling in the brain.

    Evidence PANX1 and P2RY12 knockout mice, two-photon imaging, microglial depletion/repopulation, pharmacological blockade

    PMID:34489419

    Open questions at the time
    • Identity of the specific purine species released (ATP vs. ADP vs. adenosine) was not resolved
    • Upstream stimulus for microglial PANX1 opening in vivo was not determined
  10. 2021 Medium

    Additional PANX1 missense variants (p.Ser238Pro, p.Arg300Gln) causing aberrant glycosylation and gain-of-function channel activation leading to oocyte death after fertilization extended the spectrum of PANX1 channelopathy to female infertility.

    Evidence WES, glycosylation Western blot, in vitro fertilization of mouse oocytes expressing mutant PANX1

    PMID:33495594

    Open questions at the time
    • Whether the oocyte death is ATP-efflux-dependent or due to pore-mediated osmotic lysis was not distinguished
    • Limited number of affected families
  11. 2022 Medium

    Establishment of the TLR2→caspase-5→PANX1→ATP→NLRP3 inflammasome signaling cascade in macrophages during kidney injury defined a specific innate immune activation pathway channeled through PANX1 cleavage by a non-canonical caspase.

    Evidence TLR2 KO/KD, caspase-5 inhibition, PANX1 blockade, NLRP3 activation assays in macrophages stimulated with necrotic tubular cell medium

    PMID:35473933

    Open questions at the time
    • Direct demonstration of caspase-5 cleavage of PANX1 at a specific site was not shown
    • In vivo validation in caspase-5 KO animals was not performed
  12. 2022 Medium

    Cholesterol depletion decreased PANX1 lateral diffusion but enhanced channel activity, revealing that membrane lipid composition is a biophysical regulator of PANX1 gating independent of canonical protein-based activation.

    Evidence FRAP, electrophysiology, dye uptake, ATP release in astrocytes and transfected cells with Panx1-null controls

    PMID:36291086

    Open questions at the time
    • Whether cholesterol binds PANX1 directly or acts indirectly through membrane mechanics was not resolved
    • Physiological conditions that alter membrane cholesterol around PANX1 were not identified
  13. 2023 Medium

    Cell-type-specific knockouts revealed that both astrocytic and neuronal PANX1 are required for hippocampal LTP, LTD, and spatial memory consolidation, demonstrating a non-redundant role for PANX1 in synaptic plasticity across cell types.

    Evidence Global and cell-type specific Panx1 KO mice, 8-arm radial maze, field potential recordings

    PMID:37365910

    Open questions at the time
    • Which purinergic receptor mediates PANX1-dependent LTP (as opposed to LTD) was not identified
    • Whether astrocytic PANX1 acts through ATP release or a different mechanism was not resolved
  14. 2023 Medium

    PANX1-dependent NLRP3 inflammasome activation in breast cancer cells was shown to drive doxorubicin chemoresistance through IL-1β, establishing a tumor-intrinsic pro-survival function of PANX1 signaling.

    Evidence siRNA/pharmacological PANX1 inhibition, NLRP3 and IL-1β assays, in vitro/in vivo resistance models with IL-1β rescue

    PMID:41765358

    Open questions at the time
    • Mechanism of PANX1 activation by doxorubicin was not determined
    • Whether PANX1 inhibition sensitizes tumors in patients was not tested
  15. 2024 High

    Elucidation of the niNMDAR→Src→PANX1→ATP→P2X4R pathway at hippocampal synapses resolved how conformational (non-ionotropic) NMDAR signaling is transduced into long-term depression through a purinergic relay.

    Evidence Whole-cell patch clamp in rat hippocampal slices, differential NMDAR blockade, PANX1/P2X4R pharmacology, ATP rescue

    PMID:39709529

    Open questions at the time
    • Specific Src phosphorylation site(s) on PANX1 driving channel opening were not mapped
    • Whether this pathway operates at other synapse types was not tested
  16. 2024 High

    Cardiomyocyte-specific PANX1 deletion shifted metabolism toward glycolysis and away from oxidative phosphorylation, protecting against hypertrophy, revealing that PANX1-mediated ATP efflux regulates intracellular metabolic balance in the heart.

    Evidence Cardiomyocyte-specific Panx1 KO mice, Seahorse metabolic assays, isoproterenol treatment, immune cell flow cytometry

    PMID:38957990

    Open questions at the time
    • Whether the metabolic shift is a direct consequence of ATP depletion or involves purinergic autocrine signaling was not distinguished
    • Long-term cardiac functional consequences were not fully characterized
  17. 2024 Medium

    TNFα-induced caspase-8/3 cleavage of PANX1 during immunogenic cell death was shown to drive ATP release that activates P2RX7-dependent dendritic cell maturation and antitumor T-cell responses, defining PANX1 as an effector of 'find-me' signaling in cancer immunotherapy contexts.

    Evidence PANX1 cleavage Western blot, caspase inhibitors, ATP assays, in vivo tumor models with P2RX7 inhibition, DC/T-cell activation assays

    PMID:38195677

    Open questions at the time
    • Specific caspase cleavage site(s) responsible were not mapped by mutagenesis
    • Relevance to human tumor immunotherapy was not tested
  18. 2024 Medium

    PANX1-mediated ATP release downstream of HSF1-driven transcription was shown to activate hepatic P2Y→Akt→FOXO1 and calmodulin→JNK pathways, establishing PANX1 as a metabolic effector suppressing gluconeogenesis and lipogenesis in the liver.

    Evidence Co-IP/MS, adenovirus/AAV overexpression and knockdown in vivo, PANX1 global KO mice, metabolic tolerance tests

    PMID:38937853

    Open questions at the time
    • Direct evidence that ATP (rather than another PANX1-permeable molecule) mediates the hepatic effects was not provided
    • Whether the FAM3A–HSF1–PANX1 axis operates in human liver was not confirmed
  19. 2024 Medium

    Neuronal PANX1 was shown to drive inflammatory pain sensitization through cell-autonomous effects on DRG neuron excitability, neurite outgrowth, and Wnt/β-catenin signaling, separating neuronal from glial contributions.

    Evidence Neuron-specific and glia-specific Panx1 conditional KO mice, von Frey, patch clamp, calcium imaging, Sholl analysis

    PMID:38685116

    Open questions at the time
    • Whether PANX1-dependent Wnt signaling is ATP-efflux-mediated or involves direct protein interactions was not resolved
    • Specific purinergic receptor on sensory neurons was not identified
  20. 2025 High

    Cryo-EM structures revealed that the heptameric PANX1 pore is gated by conformational plasticity of seven W74 side chains at the extracellular entrance, switching between constricted (Cl⁻-permissive) and dilated (ATP-permissive) states via cation-π interactions with R75, and that mefloquine binds a side tunnel to positively modulate ion flow — providing the first atomic-resolution gating model.

    Evidence Cryo-EM structure determination, W74/R75 mutagenesis, electrophysiology, mefloquine binding site identification

    PMID:41381453

    Open questions at the time
    • Structure of the caspase-cleaved or Src-phosphorylated activated state was not captured
    • How intracellular Cys346 communicates with the extracellular gate was not structurally resolved
  21. 2025 High

    A truncated PANX1 variant (1-89) found in metastatic breast cancer forms a constitutively active ATP-release channel independently of full-length PANX1, indicating that the minimal pore architecture resides in the first 89 residues and raising the possibility of disease-relevant gain-of-function truncations.

    Evidence Electrophysiology, ATP release, pharmacological inhibitor profiling in cells expressing Panx1-1-89 alone

    PMID:40087867

    Open questions at the time
    • Oligomeric state of the 1-89 truncation was not determined
    • In vivo relevance to metastatic progression was not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis of caspase-cleaved and Src-phosphorylated PANX1 activation; how Cys346 communicates with the W74 extracellular gate; tissue-specific pathogenic mechanisms underlying the multisystem PANX1 channelopathy; and whether pharmacological PANX1 modulation can be therapeutically exploited in neuroinflammation, pain, or cancer.
  • No activated-state structure available
  • No clinical trials targeting PANX1
  • Tissue-specific pathophysiology of Mendelian variants unexplained

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 4 GO:0008092 cytoskeletal protein binding 1
Localization
GO:0005886 plasma membrane 5
Pathway
R-HSA-112316 Neuronal System 4 R-HSA-168256 Immune System 4 R-HSA-1430728 Metabolism 3 R-HSA-162582 Signal Transduction 3 R-HSA-5357801 Programmed Cell Death 2
Partners
ACTR3CASP3CASP8P2RX4P2RX7P2RY12SRCTGM2

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2013 Cortical spreading depression (CSD) causes neuronal PANX1 megachannel opening followed by caspase-1 activation and HMGB1 release from neurons, and NF-κB activation in astrocytes; suppression of this cascade abolished CSD-induced trigeminovascular activation and headache. Pharmacological blockade of PANX1 channels in vivo, genetic mouse models, measurement of HMGB1 release, NF-κB activation assays, and dural mast cell degranulation readouts Science High 23449592
2017 PANX1 forms a pore complex with P2X7 receptor; genetic loss of P2X7 or pharmacological inhibition of the P2X7-PANX1 complex inhibits spreading depolarization, reduces neuroinflammatory cytokines (IL-1β, iNOS, COX-2), and suppresses trigeminovascular activation markers. Genetic knockout of P2x7, pharmacological pore inhibitors in wild-type and FHM1 R192Q knock-in mice, electrophysiology, cytokine quantification, CGRP and c-Fos immunostaining Brain High 28430869
2013 The food dye FD&C Blue No. 1 (BB FCF) selectively inhibits PANX1 channels with an IC50 of 0.27 µM and has no significant effect on P2X7 receptor at concentrations up to 100 µM, establishing it as a selective PANX1 pharmacological tool. Electrophysiology and dye-uptake assays comparing Panx1 channel and P2X7R activity in the presence of BB FCF and FD&C Green No. 3 The Journal of general physiology High 23589583
2010 Intracellular cysteine 346 (Cys-346) of PANX1 is essential for channel regulation; Cys346Ser substitution produces a constitutively leaky hemichannel leading to cell death, while mutation of other intracellular cysteines does not significantly alter channel properties. Site-directed mutagenesis, dye uptake assays, electrophysiology in Xenopus oocytes and N2A cells The Journal of biological chemistry High 20829356
2016 A homozygous PANX1 missense variant (p.Arg217His) causes loss-of-function of the ATP release channel, demonstrated by reduced dye uptake, ATP release, and electrophysiological currents, and is associated with multisystem human disease (intellectual disability, hearing loss, skeletal defects, primary ovarian failure). Whole exome sequencing, dye uptake, ATP release assays, electrophysiology, glycosylation analysis in multiple cell lines (HeLa, N2A, HEK293T, Ad293) The Journal of biological chemistry High 27129271
2021 Microglial PANX1 channels release purines that activate P2RY12 receptors on capillary-associated microglia (CAMs) to regulate brain capillary structure and vascular function; PANX1-/- mice phenocopy P2RY12-/- mice with capillary dilation, increased blood flow, and impaired vasodilation. PANX1 knockout and P2RY12 knockout mouse models, two-photon imaging, microglial depletion/repopulation, pharmacological blockade, molecular and ultrastructural characterization Nature communications High 34489419
2022 TLR2 signaling in macrophages activates PANX1 channels via caspase-5, enabling ATP secretion through PANX1 that in turn activates the NLRP3 inflammasome during acute kidney injury. Conditioned medium from necrotic tubular epithelial cells applied to macrophages, TLR2 knockout/knockdown, caspase-5 inhibition, PANX1 channel blockade, NLRP3 inflammasome activation assays Cell death discovery Medium 35473933
2024 TNFα promotes PANX1 cleavage via a caspase-8/3-dependent pathway to enhance ATP release and trigger P2RX7-mediated antitumor immune responses during chemotherapy-induced immunogenic cell death in colorectal cancer. Western blot of PANX1 cleavage, caspase inhibitor assays, ATP release measurements, in vivo tumor models with P2RX7 inhibition, dendritic cell maturation and T-cell activation assays Cell death & disease Medium 38195677
2013 PANX1 interacts with endogenous actin and actin-related protein 3 (Arp3) in neural stem/progenitor cells, and this interaction affects both PANX1 plasma membrane stability and cytoskeletal remodeling, with Panx1 regulating cell migration and neurite extension. Co-immunoprecipitation of endogenous proteins, scratch wound assay, neurite extension assay in neural stem/progenitor cells Cell communication and signaling Medium 23964896
2014 Panx1 loss in keratinocytes increases their migration, while loss in dermal fibroblasts increases proliferation, reduces collagen gel contraction, and abolishes TGF-β-induced α-smooth muscle actin upregulation; Panx1 knockout mice exhibit delayed wound healing. Panx1 knockout mice, scratch wound assay, proliferation assay, collagen gel contraction, TGF-β stimulation, probenecid pharmacological blockade The Journal of investigative dermatology Medium 24522432
2019 PANX1 preferentially localizes to the apical membrane domain of polarized epithelial cells; the cell surface-targeting domain maps to residues 307–379, and a tyrosine-based sorting motif (YxxØ, Y308) mutation or C-terminal truncation (Δ379) causes loss of polarity and epithelial-to-mesenchymal transition-like phenotype. GFP-tagged PANX1 in polarized MDCK cells and spheroids, mutagenesis of sorting motifs, fluorescence microscopy, cell polarization assays Experimental cell research Medium 31102595
2024 Non-ionotropic NMDA receptor (niNMDAR) signaling activates PANX1 via Src kinase; Panx1 then releases ATP (not Ca2+) to activate postsynaptic P2X4 receptors, producing long-term depression (LTD) at CA3-CA1 hippocampal synapses. Whole-cell patch clamp in rat hippocampal slices, differential NMDAR blockade (continuous vs. transient MK-801/D-APV), pharmacological blockade of PANX1 and P2X4R (5-BDBD), ATP rescue experiments The Journal of physiology High 39709529
2024 Cardiomyocyte PANX1 mediates isoproterenol-induced ATP release and Yo-Pro-1 uptake; PANX1 deletion in cardiomyocytes shifts metabolism toward glycolysis, protects against cardiac hypertrophy, and reduces neutrophil recruitment to the myocardium. Cardiomyocyte-specific Panx1 knockout mice (Panx1MyHC6), isoproterenol treatment, pharmacological blockade with spironolactone, siRNA knockdown, Seahorse metabolic assay, flow cytometry of immune cells Circulation research High 38957990
2024 FAM3A stimulates PANX1 expression via heat shock factor 1 (HSF1); PANX1-mediated ATP release activates the Akt-FOXO1 pathway via P2Y receptors to inhibit hepatic gluconeogenesis, and activates calmodulin to inhibit JNK/AP1-driven fatty acid synthase expression, suppressing lipogenesis. Co-immunoprecipitation/MS identifying protein-protein interactions, adenovirus/AAV-mediated overexpression and knockdown in vivo, PANX1 global KO mice, metabolic tolerance tests, ATP release assays Military Medical Research Medium 38937853
2022 Cholesterol depletion (via methyl-β-cyclodextrin or lovastatin) decreases lateral diffusion of PANX1 in the plasma membrane and enhances PANX1 channel activity (dye uptake, ATP release, and ionic current), linking membrane cholesterol composition to PANX1 channel regulation. FRAP for membrane mobility, electrophysiology, dye uptake, ATP release assays in astrocytes and Panx1-transfected cells, with and without Panx1 null controls Cells Medium 36291086
2023 Both astrocyte and neuronal PANX1 contribute to long-term spatial reference memory consolidation; Panx1-null mice show attenuated LTP and LTD at Schaffer collateral–CA1 synapses without changes in basal synaptic transmission. Global and cell-type specific Panx1 knockout mice, 8-arm radial maze, field potential recordings of LTP and LTD in hippocampal slices ASN neuro Medium 37365910
2024 Neuronal PANX1 drives peripheral sensitization in inflammatory pain through cell-autonomous effects on neuronal excitability, neurite outgrowth, and Wnt/β-catenin signaling; neuron-specific Panx1 deletion reduces pain sensitivity, DRG neuron excitability, and ATP-evoked Ca2+ responses following CFA injection. Global and neuron/glia-specific Panx1 conditional KO mice, von Frey test, patch clamp, EtBr dye uptake, calcium imaging, Sholl analysis, β-gal staining, qRT-PCR Military Medical Research Medium 38685116
2021 Homozygous PANX1 missense variants (p.Ser238Pro and p.Arg300Gln) alter PANX1 glycosylation pattern and cause aberrant PANX1 channel activation, leading to oocyte death after fertilization in vitro. Whole exome sequencing, Western blot of glycosylation, in vitro fertilization of mouse oocytes expressing mutant PANX1 European journal of human genetics Medium 33495594
2024 Heterozygous PANX1 variants alter glycosylation pattern and cause aberrant channel activation, affecting ATP release and membrane electrophysiological properties, demonstrated directly in human oocytes. Western blot of glycosylation in HeLa cells, ATP release assay, electrophysiology, in vitro fertilization of human and mouse oocytes Journal of ovarian research Medium 39232764
2025 Cryo-EM structural analysis reveals that PANX1 pore gating is controlled by structural plasticity at the extracellular entrance formed by seven W74 residues whose side chains can sample a constricted (chloride-permissive) or dilated (ATP-permissive) state, coupled to cation-π interactions with R75; mefloquine binds near the side tunnel as a positive modulator to enhance ion flow. Cryo-EM structure determination, mutagenesis of W74 and R75, electrophysiology, identification of mefloquine binding site Nature communications High 41381453
2025 A truncated PANX1 mutant (Panx1-1-89) enriched in metastatic breast cancer cells forms a constitutively active ATP release channel on its own, retaining sensitivity to high extracellular K+ and to most wild-type PANX1 channel inhibitors. Electrophysiology, ATP release assays, pharmacological inhibitor sensitivity testing in cells expressing Panx1-1-89 without co-expressed wild-type Panx1 The FEBS journal High 40087867
2024 PANX1 protein interacts with TGM2; TGM2 binding to PANX1 promotes lipid deposition in kidney cells, and pharmacological inhibition or knockdown of PANX1 decreases PPARα and PANK1 levels, linking PANX1 to lipid metabolism regulation. Co-immunoprecipitation, siRNA knockdown, TGM2 overexpression, Western blot of PPARα and PANK1 in adriamycin nephropathy model Translational research Low 38734063
2024 PANX1 deletion in cardiomyocytes increases glycolytic ATP production and decreases oxidative phosphorylation, demonstrating that PANX1 channel activity regulates the balance between glycolytic and oxidative metabolism in cardiomyocytes. Cardiomyocyte-specific Panx1 KO mice, Seahorse XF metabolic assay, isoproterenol treatment, siRNA knockdown in H9c2 cells Circulation research Medium 38957990
2023 Doxorubicin triggers PANX1-dependent activation of the NLRP3 inflammasome and downstream IL-1β maturation in breast cancer cells, promoting adaptive chemoresistance; pharmacological or genetic PANX1 inhibition re-sensitizes resistant cells and this is reversed by exogenous IL-1β. siRNA and pharmacological inhibition of PANX1, NLRP3 inflammasome activation assays, IL-1β ELISA, in vitro and in vivo doxorubicin resistance models, rescue with exogenous IL-1β Cancer letters Medium 41765358
2025 ATP triggers macropinocytosis in neuroblastoma cells in a PANX1-dependent manner, driving cell size increase; mutation of the extracellular tryptophan W74 in PANX1 abolishes ATP-evoked cell area enlargement, and PANX1 itself is internalized to macropinosomes during this process. W74 mutagenesis, ARF6 Q67L dominant-active expression, PI3K and actin inhibitors, fluorescence imaging of PANX1 internalization and co-localization with macropinosomal cargo Biology open Medium 41250870
2024 PANX1 overexpression in granulosa cells mediates ATP efflux to the extracellular space, depletes intracellular ATP, and suppresses cell proliferation, contributing to follicular dysplasia associated with advanced maternal age. PANX1 plasmid overexpression and siRNA knockdown in KGN cells and primary granulosa cells, extracellular and intracellular ATP measurement, proliferation and apoptosis assays Reproductive biology Medium 41319607
2024 Abnormal PANX1 overexpression in endometrial stromal cells elevates extracellular ATP concentration and impairs endometrial decidualization (reduced PRL and IGFBP-1, aberrant cytoskeleton); conversely PANX1 knockdown also impairs decidualization, indicating a requirement for normal PANX1 expression levels. PANX1 overexpression and knockdown in human endometrial stromal cells, extracellular ATP assay, Western blot of decidualization markers, immunofluorescence, in vivo mouse model Scientific reports Medium 41775813

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 Spreading depression triggers headache by activating neuronal Panx1 channels. Science (New York, N.Y.) 401 23449592
2021 Capillary-associated microglia regulate vascular structure and function through PANX1-P2RY12 coupling in mice. Nature communications 232 34489419
2001 RGS-PX1, a GAP for GalphaS and sorting nexin in vesicular trafficking. Science (New York, N.Y.) 185 11729322
2017 Inhibition of the P2X7-PANX1 complex suppresses spreading depolarization and neuroinflammation. Brain : a journal of neurology 100 28430869
2013 The food dye FD&C Blue No. 1 is a selective inhibitor of the ATP release channel Panx1. The Journal of general physiology 78 23589583
2008 Patch-clamp coordinated spectroscopy shows P2X2 receptor permeability dynamics require cytosolic domain rearrangements but not Panx-1 channels. Proceedings of the National Academy of Sciences of the United States of America 72 18689682
2016 A Germline Variant in the PANX1 Gene Has Reduced Channel Function and Is Associated with Multisystem Dysfunction. The Journal of biological chemistry 63 27129271
2013 Panx1 regulates neural stem and progenitor cell behaviours associated with cytoskeletal dynamics and interacts with multiple cytoskeletal elements. Cell communication and signaling : CCS 61 23964896
2014 Panx1 regulates cellular properties of keratinocytes and dermal fibroblasts in skin development and wound healing. The Journal of investigative dermatology 59 24522432
2006 Essential role of RGS-PX1/sorting nexin 13 in mouse development and regulation of endocytosis dynamics. Proceedings of the National Academy of Sciences of the United States of America 51 17077144
2015 Prenatal exposure to inflammatory conditions increases Cx43 and Panx1 unopposed channel opening and activation of astrocytes in the offspring effect on neuronal survival. Glia 50 26096155
2016 P2X7R-Panx1 Complex Impairs Bone Mechanosignaling under High Glucose Levels Associated with Type-1 Diabetes. PloS one 48 27159053
1990 Two group I mitochondrial introns in the cob-box and coxI genes require the same MRS1/PET157 nuclear gene product for splicing. Current genetics 47 1699677
2003 2-Cys peroxiredoxin PfTrx-Px1 is involved in the antioxidant defence of Plasmodium falciparum. Molecular and biochemical parasitology 45 12946843
1986 Cloning of a nuclear gene MRS1 involved in the excision of a single group I intron (bI3) from the mitochondrial COB transcript in S. cerevisiae. Current genetics 42 2834089
1996 Effect of vitamin E on human glutathione peroxidase (GSH-PX1) expression in cardiomyocytes. Free radical biology & medicine 39 8886791
2024 TNFα modulates PANX1 activation to promote ATP release and enhance P2RX7-mediated antitumor immune responses after chemotherapy in colorectal cancer. Cell death & disease 38 38195677
1987 A yeast nuclear gene, MRS1, involved in mitochondrial RNA splicing: nucleotide sequence and mutational analysis of two overlapping open reading frames on opposite strands. The EMBO journal 36 2443348
2022 TLR2/caspase-5/Panx1 pathway mediates necrosis-induced NLRP3 inflammasome activation in macrophages during acute kidney injury. Cell death discovery 35 35473933
2014 Prenatal nicotine exposure enhances Cx43 and Panx1 unopposed channel activity in brain cells of adult offspring mice fed a high-fat/cholesterol diet. Frontiers in cellular neuroscience 35 25520621
2010 Intracellular cysteine 346 is essentially involved in regulating Panx1 channel activity. The Journal of biological chemistry 35 20829356
2016 Parental vitamin D deficiency during pregnancy is associated with increased blood pressure in offspring via Panx1 hypermethylation. American journal of physiology. Heart and circulatory physiology 33 27769995
2017 Possible roles for ATP release from RBCs exclude the cAMP-mediated Panx1 pathway. American journal of physiology. Cell physiology 31 28855161
2022 Mechanisms of Pannexin 1 (PANX1) Channel Mechanosensitivity and Its Pathological Roles. International journal of molecular sciences 28 35163442
2015 Normal Taste Acceptance and Preference of PANX1 Knockout Mice. Chemical senses 27 25987548
2010 Cloning and characterization of a xylanase, KRICT PX1 from the strain Paenibacillus sp. HPL-001. Biotechnology advances 22 20493247
2019 Panx1 promotes invasion-metastasis cascade in hepatocellular carcinoma. Journal of Cancer 21 31737105
2021 Homozygous variants in PANX1 cause human oocyte death and female infertility. European journal of human genetics : EJHG 20 33495594
2010 Splicing of yeast aI5beta group I intron requires SUV3 to recycle MRS1 via mitochondrial degradosome-promoted decay of excised intron ribonucleoprotein (RNP). The Journal of biological chemistry 20 20064926
1992 The MRS1 gene of S. douglasii: co-evolution of mitochondrial introns and specific splicing proteins encoded by nuclear genes. Gene expression 20 1333316
2018 A Potential Compensatory Role of Panx3 in the VNO of a Panx1 Knock Out Mouse Model. Frontiers in molecular neuroscience 19 29780304
2017 Genetic deletion of microglial Panx1 attenuates morphine withdrawal, but not analgesic tolerance or hyperalgesia in mice. Channels (Austin, Tex.) 18 28745932
2016 Loss of Panx1 Impairs Mammary Gland Development at Lactation: Implications for Breast Tumorigenesis. PloS one 18 27099931
2024 Cardiomyocyte PANX1 Controls Glycolysis and Neutrophil Recruitment in Hypertrophy. Circulation research 17 38957990
2022 High PANX1 Expression Leads to Neutrophil Recruitment and the Formation of a High Adenosine Immunosuppressive Tumor Microenvironment in Basal-like Breast Cancer. Cancers 17 35884429
2017 Manipulation of Panx1 Activity Increases the Engraftment of Transplanted Lacrimal Gland Epithelial Progenitor Cells. Investigative ophthalmology & visual science 17 29098296
2017 Mouse Panx1 Is Dispensable for Hearing Acquisition and Auditory Function. Frontiers in molecular neuroscience 16 29234270
2010 The Mrs1 splicing factor binds the bI3 group I intron at each of two tetraloop-receptor motifs. PloS one 16 20126554
2000 Site-directed mutagenesis of the yeast resolving enzyme Cce1 reveals catalytic residues and relationship with the intron-splicing factor Mrs1. The Journal of biological chemistry 16 10825168
2021 Design and synthesis of the first indole-based blockers of Panx-1 channel. European journal of medicinal chemistry 15 34174741
2014 Investigation of olfactory function in a Panx1 knock out mouse model. Frontiers in cellular neuroscience 15 25309319
2022 Panx1 channels promote both anti- and pro-seizure-like activities in the zebrafish via p2rx7 receptors and ATP signaling. Communications biology 14 35585187
2021 Alteration of Cx37, Cx40, Cx43, Cx45, Panx1, and Renin Expression Patterns in Postnatal Kidneys of Dab1-/- (yotari) Mice. International journal of molecular sciences 14 33525532
2022 New Panx-1 Blockers: Synthesis, Biological Evaluation and Molecular Dynamic Studies. International journal of molecular sciences 13 35563213
2024 Cx43 hemichannels and panx1 channels contribute to ethanol-induced astrocyte dysfunction and damage. Biological research 12 38576018
2022 Defining Steric Requirements at CB1 and CB2 Cannabinoid Receptors Using Synthetic Cannabinoid Receptor Agonists 5F-AB-PINACA, 5F-ADB-PINACA, PX-1, PX-2, NNL-1, and Their Analogues. ACS chemical neuroscience 12 35404067
2024 PANX1-mediated ATP release confers FAM3A's suppression effects on hepatic gluconeogenesis and lipogenesis. Military Medical Research 11 38937853
2023 Astrocyte and Neuronal Panx1 Support Long-Term Reference Memory in Mice. ASN neuro 11 37365910
2024 The small molecule raptinal can simultaneously induce apoptosis and inhibit PANX1 activity. Cell death & disease 10 38336804
2021 Inhibiting of circ-TLK1 inhibits the progression of glioma through down-regulating PANX1 via targeting miR-17-5p. Journal of molecular histology 10 34181173
2011 Design and synthesis of a quintessential self-transmissible IncX1 plasmid, pX1.0. PloS one 10 21625636
2019 Destination and consequences of Panx1 and mutant expression in polarized MDCK cells. Experimental cell research 9 31102595
2024 Non-ionotropic NMDAR signalling activates Panx1 to induce P2X4R-dependent long-term depression in the hippocampus. The Journal of physiology 8 39709529
2023 Structure-Based Design and Synthesis of Stapled 10Panx1 Analogues for Use in Cardiovascular Inflammatory Diseases. Journal of medicinal chemistry 8 37703077
2022 Activity and Stability of Panx1 Channels in Astrocytes and Neuroblastoma Cells Are Enhanced by Cholesterol Depletion. Cells 8 36291086
2020 Phase I metabolism of synthetic cannabinoid receptor agonist PX-1 (5F-APP-PICA) via incubation with human liver microsomes and UHPLC-HRMS. Biomedical chromatography : BMC 8 31863591
2019 P2X7R and PANX-1 channel relevance in a zebrafish larvae copper-induced inflammation model. Comparative biochemistry and physiology. Toxicology & pharmacology : CBP 8 31136852
2024 miR-224-5p alleviates preeclampsia-like mouse symptoms by targeting PANX1 to inhibit ferroptosis in trophoblast cells. Placenta 7 39426351
2019 Ablation of both Cx40 and Panx1 results in similar cardiovascular phenotypes exhibited in Cx40 knockout mice. Bioscience reports 7 30745457
2024 Glial Cx43 hemichannels and neuronal Panx1 hemichannels and P2X7 receptors orchestrate presynaptic homeostatic plasticity. Cellular signalling 6 38395185
2024 Propofol Triggers Cell Death in Lung Cancer Cells by Increasing PANX1 Expression, Activating the Mitochondrial Cell Death Pathway, and Enhancing ROS Levels. Discovery medicine 6 39600278
2023 Inhibition of PANX1 Channels Reduces the Malignant Properties of Human High-Risk Neuroblastoma. Journal of Cancer 6 37056395
2023 Contralateral Astrocyte Response to Acute Optic Nerve Damage Is Mitigated by PANX1 Channel Activity. International journal of molecular sciences 6 37958624
2022 A novel heterozygous variant in PANX1 is associated with oocyte death and female infertility. Journal of assisted reproduction and genetics 6 35834089
2021 The Contribution of Astrocyte and Neuronal Panx1 to Seizures Is Model and Brain Region Dependent. ASN neuro 6 33910381
2024 Counteracting TGM2 by a Fibroin peptide ameliorated Adriamycin-induced nephropathy via regulation of lipid metabolism through PANX1-PPAR α/PANK1 pathway. Translational research : the journal of laboratory and clinical medicine 5 38734063
2024 A novel heterozygous missense variant of PANX1 causes human oocyte death and female infertility. Journal of ovarian research 5 39232764
2023 Elabela-apelin-12, 17, 36/APJ system promotes platelet aggregation and thrombosis via activating the PANX1-P2X7 signaling pathway. Journal of cellular biochemistry 5 36855998
2022 A novel heterozygous variant in PANX1 causes primary infertility due to oocyte death. Journal of assisted reproduction and genetics 5 36469255
2024 Neuronal Panx1 drives peripheral sensitization in experimental plantar inflammatory pain. Military Medical Research 4 38685116
2023 Cx43 Hemichannel and Panx1 Channel Modulation by Gap19 and 10Panx1 Peptides. International journal of molecular sciences 4 37511370
2023 Loss of Panx1 function in zebrafish alters motor behavior in a lab-on-chip model of Parkinson's disease. Journal of neuroscience research 4 37688406
2022 The Interplay of Cx26, Cx32, Cx37, Cx40, Cx43, Cx45, and Panx1 in Inner-Ear Development of Yotari (dab1-/-) Mice and Humans. Biomedicines 4 35327391
2021 [Mechanism of Chuanxiong Rhizoma intervention on central sensitization of Panx1-Src-NMDAR-2B signaling pathway in neuropathic pain model rats]. Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica 4 34467730
2025 Synthesis of 3-Carboxy-6-sulfamoylquinolones and Mefloquine-Based Compounds as Panx1 Blockers: Molecular Docking, Electrophysiological and Cell Culture Studies. Molecules (Basel, Switzerland) 3 40430343
1979 Cis- and trans-activity of P22 antirepressor protein against c-repression specified by the closely related Salmonella phages L and Px1. Molecular & general genetics : MGG 3 374992
2024 Apically localized PANX1 impacts neuroepithelial expansion in human cerebral organoids. Cell death discovery 2 38212304
2024 Novel genetic variants in the NLRP3 inflammasome-related PANX1 and APP genes predict survival of patients with hepatitis B virus-related hepatocellular carcinoma. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 2 39090420
2024 The Ethanolic Extract of Polygala paniculata L. Blocks Panx1 Channels and Reduces Ischemic Brain Infarct in a Dose- and Sex-Dependent Way. Molecular neurobiology 2 39271622
2023 Astrocyte and neuronal Panx1 support long-term reference memory in mice. bioRxiv : the preprint server for biology 2 36711845
2023 Panx1 knockout promotes preneoplastic aberrant crypt foci development in a chemically induced model of mouse colon carcinogenesis. International journal of experimental pathology 2 37594023
2025 Metabolomics and mass spectrometry imaging reveal the effect of Prunella vulgaris oil on chronic pelvic inflammatory disease: Exploring the mechanism from inhibition of PANX1. Journal of ethnopharmacology 1 40783103
2025 The impact of Panx1 on inflammation, immunity, and cancer: a comprehensive review. Frontiers in medicine 1 40978734
2025 Tanshinone IIA Inhibits Microglial Activation and Inflammation and Relieves Cerebral Ischemia‒Reperfusion Injury Through TGM2/PANX1. Biochemical genetics 1 41351813
2025 Structural basis of PANX1 permeation and positive modulation by mefloquine. Nature communications 1 41381453
2024 Potentially functional variants of CHMP4A and PANX1 in the pyroptosis-related pathway predict survival of patients with non-oropharyngeal head and neck squamous cell carcinoma. Molecular carcinogenesis 1 38860607
2024 Cold Exposure Rejuvenates the Metabolic Phenotype of Panx1 Mice. Biomolecules 1 39334824
2023 Differential activation of mouse and human Panx1 channel variants. PloS one 1 38100403
2022 [Colonization performance and pyrene degradation characteristics of Stenotrophomonas maltophilia PX1]. Ying yong sheng tai xue bao = The journal of applied ecology 1 36131672
2018 [Sleep-wake cycle and experimental models of Panx1 mutations]. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova 1 30698564
2026 Identification and validation of PANX1 as an inflammasome-related biomarker in gestational diabetes mellitus: insights from machine learning and experimental approaches. Mammalian genome : official journal of the International Mammalian Genome Society 0 41543551
2026 PANX1-mediated NLRP3 inflammasome activation promotes an adaptive doxorubicin resistance through IL-1β signaling in breast cancer. Cancer letters 0 41765358
2026 Abnormal elevated PANX1 expression hampers endometrial decidualization by upregulating extracellular ATP concentration in patients with recurrent implantation failure. Scientific reports 0 41775813
2025 A metastasis-associated pannexin-1 mutant (Panx11-89) forms a minimalist ATP release channel. The FEBS journal 0 40087867
2025 The Synergistic Role of P2rx7 and Panx1 in Regulating Alveolar Macrophage Pyroptosis and Exosome-Mediated Ferroptosis of Alveolar Epithelial Cells in Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 0 40827894
2025 Electroacupuncture ameliorates mitochondrial dysfunction and alleviates traumatic brain injury via the PANX1/ATP/Ca2+ pathway. Behavioural brain research 0 41197910
2025 ATP increases murine neuroblastoma cell size through a PANX1- and macropinocytosis-dependent mechanism. Biology open 0 41250870
2025 Downregulation of intracellular ATP levels by PANX1 inhibits ovarian granulosa cell proliferation and mediates follicular dysplasia in elderly women. Reproductive biology 0 41319607
2024 A metastasis-associated Pannexin1 mutant (Panx1 1-89 ) forms a minimalist ATP release channel. bioRxiv : the preprint server for biology 0 38559162
2013 [Distribution and regulation of Panx1 protein]. Sheng li ke xue jin zhan [Progress in physiology] 0 24027825