Affinage

Showing PECAM1 — CD31 is a alias.

PECAM1

Platelet endothelial cell adhesion molecule · UniProt P16284

Length
738 aa
Mass
82.5 kDa
Annotated
2026-06-10
100 papers in source corpus 36 papers cited in narrative 35 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PECAM-1 (CD31) is a six-Ig-domain transmembrane glycoprotein that concentrates at endothelial intercellular junctions and on leukocyte and platelet surfaces, where it mediates calcium-dependent homophilic cell-cell adhesion and functions as a junctional signaling and mechanotransduction hub (PMID:1690453, PMID:2351935, PMID:1874786, PMID:26702061). It self-associates as a monomer/dimer-equilibrium glycoprotein whose IgD1 and IgD2 domains form the trans-homophilic binding interface (PMID:10425179, PMID:26702061), and its cytoplasmic tail couples it to the cytoskeleton and the β-catenin/VE-cadherin adherens-junction complex to support endothelial tube formation, barrier integrity, and modulation of β-catenin signaling (PMID:1429859, PMID:9120301, PMID:10462517, PMID:7589563). A central, well-defined role is the control of leukocyte transendothelial migration: PECAM-1 homophilic engagement mediates a distinct diapedesis step in vitro and in vivo (PMID:7722409), and physical traction on endothelial PECAM-1 during transmigration activates a PECAM-1–VE-cadherin–VEGFR2 mechanotransduction complex that releases SHP2 to dephosphorylate VE-cadherin at Y731, destabilizing junctions in a Ca2+-, myosin II-, and tension-dependent manner (PMID:33604918, PMID:37643615). Under laminar shear, PECAM-1 transduces flow by recruiting SHP2 and transactivating Tie2 and Gab1 to drive ERK1/2/Akt/eNOS signaling, and is required for flow-induced vascular remodeling (PMID:15985432, PMID:26706435, PMID:19390054). Its dual ITIM cytoplasmic tyrosines support diverse outputs: activation of Rap1 to upregulate integrin-mediated adhesion (PMID:10725328), Erk/Akt-dependent suppression of FoxO3-driven apoptosis (PMID:26392551), glycolytic reprogramming via SHP/Akt/FoxO1/cMyc for barrier recovery (PMID:32681081), and recruitment of SHP-1 in dendritic cells to limit immune activation (PMID:24616502). PECAM-1 also serves as a receptor exploited by pathogens, binding Plasmodium falciparum-infected erythrocytes and acting as the endothelial receptor for Clostridium perfringens β-toxin through its Ig6 domain (PMID:9396614, PMID:32497498), and partners with PIEZO1 to direct Ca2+-dependent junctional remodeling (PMID:37005489). On viable leukocytes its homophilic ligation transmits detachment signals that are disabled upon apoptosis, switching the molecule toward promoting macrophage engulfment (PMID:12110892).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1990 High

    Establishing the molecular identity of PECAM-1 defined it as a junctional Ig-superfamily cell adhesion molecule, framing all subsequent functional study.

    Evidence cDNA cloning and sequence analysis from an endothelial library

    PMID:1690453 PMID:2351935

    Open questions at the time
    • Cloning alone did not establish adhesive mechanism or ligand
    • No functional readout for signaling
  2. 1991 High

    Reconstitution in null cells showed PECAM-1 is itself sufficient to drive calcium-dependent cell-cell adhesion and junctional localization, establishing its adhesive function.

    Evidence Full-length cDNA transfection into COS-7/3T3/L cells with aggregation assays and antibody blocking

    PMID:1874786

    Open questions at the time
    • Did not resolve homophilic vs heterophilic binding partner
    • Cytoplasmic signaling consequences not addressed
  3. 1992 Medium

    The cytoplasmic tail was shown to be required for junctional targeting and migration modulation, and PKC-mediated serine/threonine phosphorylation was identified, linking PECAM-1 to intracellular regulation.

    Evidence Truncation transfection with migration assays; phosphoamino acid analysis with PKC inhibition across platelets, T cells, endothelium

    PMID:1429859 PMID:1544907

    Open questions at the time
    • Tyrosine phosphorylation and ITIM signaling not yet characterized
    • Downstream effectors of migration not identified
  4. 1994 Medium

    PECAM-1 was linked to cytoskeletal association upon activation and to upregulation of leukocyte integrin function, connecting junctional adhesion to inside-out signaling.

    Evidence Cytoskeletal fractionation, phosphorylation, and aggregation assays

    PMID:8017765

    Open questions at the time
    • Molecular mediator of integrin upregulation not defined
    • Cytoskeletal linker identity unknown
  5. 1995 High

    Reciprocal blocking experiments established PECAM-1 as a homophilic mediator of a distinct leukocyte diapedesis step and a contributor to endothelial barrier function, defining its central role in vascular inflammation.

    Evidence In vitro transmigration and permeability assays plus in vivo antibody blocking and vascular leakage models; cytokine-induced junctional redistribution

    PMID:7589563 PMID:7722409 PMID:7759892

    Open questions at the time
    • Signaling chain from engagement to junctional opening unknown
    • Force/mechanotransduction component not yet identified
  6. 1997 High

    PECAM-1 was integrated into the adherens-junction complex with VE-cadherin and β-catenin during tube formation and angiogenesis, and identified as an exploited receptor for malaria-infected erythrocytes.

    Evidence Tube formation/wound healing models, CD31-β-catenin Co-IP, corneal neovascularization, and infected-RBC binding assays with domain-specific blocking

    PMID:9120301 PMID:9284815 PMID:9396614

    Open questions at the time
    • Direct physical mechanism coupling PECAM-1 to actin not resolved
    • Heterophilic ligand for pRBC binding interface partial
  7. 1999 High

    Biophysical and biochemical work defined PECAM-1 as a glycosylated monomer/dimer-equilibrium protein that recruits SHP-2 and modulates β-catenin signaling and survival, establishing it as a signaling scaffold beyond adhesion.

    Evidence Analytical ultracentrifugation, cross-linking, glycan MS, Co-IP of SHP-2 and phospho-β-catenin, apoptosis and nuclear translocation assays

    PMID:10343075 PMID:10425179 PMID:10462517

    Open questions at the time
    • Functional role of SHP-2 recruitment not yet placed in a pathway
    • Survival mechanism downstream effectors undefined
  8. 2000 High

    PECAM-1 cytoplasmic signaling was shown to activate Rap1 to drive integrin-dependent T cell adhesion, and cell-type-specific genetics attributed bleeding-time control to endothelial PECAM-1.

    Evidence Rap1 GTP-loading with dominant-negative/active constructs and adhesion assays; bone marrow chimeras with tail bleeding assays in KO mice

    PMID:10725328 PMID:10880378

    Open questions at the time
    • Link between ITIM phosphorylation and Rap1 GEF activation incompletely mapped
    • Mechanism of hemostatic defect not molecularly resolved
  9. 2002 High

    Homophilic CD31 ligation was shown to transmit active detachment signals on viable leukocytes that are disabled upon apoptosis, explaining how the same molecule switches to promote macrophage clearance of dying cells.

    Evidence Flow-based macrophage binding assays comparing viable vs apoptotic leukocytes with antibody blocking

    PMID:12110892

    Open questions at the time
    • Molecular basis for the apoptotic disabling of the detachment signal unknown
    • Signaling output downstream of detachment ligation not defined
  10. 2003 Medium

    Clustering of PECAM-1 was shown to drive a distinct, non-clathrin/non-caveolar endocytic route, defining how junctional PECAM-1 is internalized and trafficked.

    Evidence Anti-PECAM conjugate internalization with pharmacological inhibitors and actin imaging

    PMID:12640043

    Open questions at the time
    • Molecular machinery of the macropinocytosis-like pathway unidentified
    • Physiological trigger for clustering-induced internalization unclear
  11. 2004 High

    Genetic and chimera experiments established endothelial junctional PECAM-1 as protective against endotoxic shock, extending its barrier role to systemic inflammation.

    Evidence LPS challenge in PECAM-1 KO mice with bone marrow chimeras

    PMID:15319204

    Open questions at the time
    • Signaling pathway mediating endothelial protection not defined here
    • Relationship to barrier vs anti-inflammatory functions unresolved
  12. 2005 High

    PECAM-1 was placed at the apex of shear-stress mechanotransduction by transactivating Tie2 via SHP2 to drive ERK/Akt/eNOS, defining it as a flow sensor.

    Evidence Reciprocal Co-IP/MS, PECAM-1 and Tie2 siRNA, and phosphorylation readouts under flow

    PMID:15985432

    Open questions at the time
    • Physical force-sensing step upstream of phosphorylation not resolved
    • How PECAM-1 distinguishes flow from other stimuli unclear
  13. 2006 High

    KSHV K5 ubiquitin ligase was shown to deplete CD31 by dual endocytic/lysosomal and ER-proteasomal routes, revealing a viral strategy targeting PECAM-1 and its impact on EC migration.

    Evidence K5 expression, ubiquitination assays, inhibitor treatments, PACS-2 interaction, and migration assays

    PMID:16601245

    Open questions at the time
    • Host physiological regulator analogous to K5 not identified
    • Consequences for junction integrity not assessed
  14. 2010 High

    Two studies clarified regulation and additional roles: TCR-driven shedding of CD31 ectodomain abolishes its inhibitory cis-oligomerization, and PECAM-1/Pyk2 interaction mediates anoikis resistance in tumor cells.

    Evidence Shedding/plasma detection with synthetic peptide rescue and ITIM/SHP2 phosphorylation assays; Co-IP with domain-deletion mutants and soft-agar assays

    PMID:20074345 PMID:20400708

    Open questions at the time
    • Protease responsible for CD31 cleavage not definitively identified
    • Pyk2 interaction interface only mapped by exon deletion
  15. 2014 High

    CD31 ITIM signaling was shown to be cytoprotective in endothelium (via Akt-mediated FoxO3 exclusion) and coinhibitory in dendritic cells (via SHP-1/NF-κB), establishing dual prosurvival and immunoregulatory roles.

    Evidence ITIM point mutants, RT-PCR arrays, FoxO3 localization, in vivo β-cell gene transfer; DC signaling manipulation with EAE adoptive transfer

    PMID:24616502 PMID:26392551

    Open questions at the time
    • Trigger that activates CD31 upon TNF receptor engagement not fully defined
    • Distinct SHP-1 vs SHP-2 selection across cell types unexplained
  16. 2015 High

    PECAM-1 mechanotransduction was deepened by showing flow-specific Gab1/Akt/eNOS activation, and the homophilic interface was defined at atomic resolution by crystallography.

    Evidence PECAM1/SHP2 siRNA with flow-vs-HGF specificity controls and KO mice; X-ray structure of IgD1-IgD2

    PMID:26702061 PMID:26706435

    Open questions at the time
    • Full-length dimer/cis-oligomer architecture not resolved by the IgD1-IgD2 structure
    • Coupling of force to conformational change unmodeled
  17. 2020 High

    PECAM-1 was shown to drive SHP/Akt/FoxO1/cMyc-dependent glycolytic reprogramming for barrier recovery, and identified as the Ig6-dependent endothelial receptor for C. perfringens β-toxin.

    Evidence Metabolic flux assays with SHP inhibition and Akt/AMPK rescue in KO mice; reconstitution in cells/liposomes with Ig-domain mapping and KO mice

    PMID:32497498 PMID:32681081

    Open questions at the time
    • How junctional disruption couples to metabolic switch upstream of SHP unclear
    • β-toxin Ig6 binding mode not structurally defined
  18. 2021 High

    The molecular chain of leukocyte diapedesis was completed by showing PECAM-1 triggers SHP2 to dephosphorylate VE-cadherin Y731 in a Ca2+-, myosin II-, and tension-dependent manner, with β-catenin masking Y731 until force is applied.

    Evidence PECAM-1 SHP2-binding and VE-cadherin Y731 mutants in vitro and in vivo with KO/knock-in mice and myosin/Ca2+ manipulation

    PMID:33604918

    Open questions at the time
    • How force is transmitted from leukocyte to the PECAM-1 complex not directly visualized here
    • Reversal/re-annealing of the junction post-diapedesis incompletely mapped
  19. 2023 High

    PECAM-1 was shown to act within a force-activated VE-cadherin–VEGFR2 mechanotransduction complex during TEM and to recruit PIEZO1 to junctions, integrating mechanical force sensing with junctional remodeling.

    Evidence FLIM traction detection, inducible endothelial VEGFR2 KO and Y1175 mutants in three inflammation models; endogenous PIEZO1 tagging, Co-IP, and domain mapping

    PMID:37005489 PMID:37643615

    Open questions at the time
    • Stoichiometry and assembly order of the PECAM-1/VE-cadherin/VEGFR2/PIEZO1 complex unresolved
    • How VEGFR2 Y1175 is phosphorylated independent of kinase activity unexplained

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single homophilic receptor integrates mechanical force, Ca2+ signaling, and ITIM-coupled phosphatase recruitment to select among barrier opening, survival, metabolic, and immunoregulatory outputs in a context-dependent manner remains unresolved.
  • No unified structural model of the force-activated junctional complex
  • Determinants selecting SHP-1 vs SHP-2 and downstream output undefined
  • Mechanism linking conformational/force state to specific signaling branch unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0060089 molecular transducer activity 3 GO:0060090 molecular adaptor activity 3 GO:0098631 cell adhesion mediator activity 3 GO:0001618 virus receptor activity 2 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-1500931 Cell-Cell communication 4 R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 4 R-HSA-1474244 Extracellular matrix organization 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-109582 Hemostasis 2
Partners
CTNNB1 (Β-CATENIN)GAB1PIEZO1PTK2B (PYK2)PTPN11 (SHP2)TIE2 (TEK)VE-CADHERIN (CDH5)VEGFR2 (KDR)
Complex memberships
PECAM-1–VE-cadherin–VEGFR2 mechanotransduction complexadherens junction (PECAM-1/VE-cadherin/β-catenin)

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 PECAM-1 (CD31) was cloned and identified as a 130-kDa integral membrane glycoprotein containing six extracellular immunoglobulin-like domains, placing it in the CAM subgroup of the Ig superfamily. Its cell surface distribution at intercellular junctions suggested participation in cellular recognition events. cDNA cloning from endothelial cell library; sequence analysis Science High 1690453 2351935
1991 PECAM-1 mediates homophilic, calcium-dependent cell-cell adhesion. When transfected into COS-7, 3T3, or L cells, PECAM-1 concentrated at cell-cell junctions (recapitulating endothelial distribution) and L-cell transfectants formed calcium-dependent aggregates inhibitable by anti-PECAM antibodies. Full-length PECAM-1 cDNA transfection into null cell lines; cell aggregation assay; anti-PECAM antibody blocking The Journal of cell biology High 1874786
1992 PECAM-1 transfected into NIH/3T3 cells localizes to sites of cell-cell contact via its full-length form (requiring the cytoplasmic tail) and diminishes cell migration rate compared to control or extracellular-domain-only transfectants, demonstrating that PECAM-1 modulates cell migration. Full-length and truncated PECAM-1 transfection into NIH/3T3 cells; quantitative migration assays; indirect immunofluorescence Journal of cellular physiology Medium 1429859
1992 CD31 becomes rapidly phosphorylated on serine/threonine residues (not tyrosine) in platelets, Jurkat T cells, and endothelial cells following cell activation. Phosphorylation is induced by phorbol ester and blocked by the PKC inhibitor staurosporin, indicating PKC-mediated phosphorylation. Following T cell activation, CD31 mRNA and protein are downregulated, partly via decreased transcription. Phosphoamino acid analysis; phorbol ester stimulation; staurosporin inhibition; nuclear run-on assay; Northern/Western blot The Journal of biological chemistry Medium 1544907
1994 PECAM-1 localizes to endothelial intercellular junctions; upon cellular activation, it becomes highly phosphorylated and associates with the cytoskeleton, enabling it to move within the membrane plane. PECAM-1-transfected L cells aggregate in a calcium- and PECAM-1-dependent manner. PECAM-1 engagement on leukocytes upregulates integrin function. Cytoskeletal fractionation; phosphorylation assays; cell aggregation assay; anti-PECAM antibody blocking Annals of the New York Academy of Sciences Medium 8017765
1995 PECAM-1 mediates a distinct transendothelial migration (diapedesis) step for neutrophils and monocytes, independent of leukocyte binding to the apical endothelial surface. Anti-PECAM-1 antibody or soluble recombinant PECAM-1 directed at either leukocyte or endothelial PECAM-1 blocked transmigration by 70–90% in vitro; antibody against mouse PECAM-1 blocked leukocyte emigration into the peritoneum in vivo. The non-additivity of leukocyte- vs. endothelial-directed reagents suggests a homophilic PECAM-1:PECAM-1 interaction. In vitro transendothelial migration assay; anti-PECAM-1 antibody/soluble PECAM-1 blocking; in vivo thioglycollate-induced peritonitis mouse model Journal of leukocyte biology High 7722409
1995 PECAM-1 contributes to endothelial barrier (vascular permeability) function: macromolecule permeability assays on monolayers expressing native or transfected PECAM-1 showed that PECAM-1 participates in establishing and maintaining the barrier. In vivo injection of anti-murine PECAM-1 monoclonal antibody caused detectable leakage of hepatic and renal blood vessels. Macromolecule permeability assays on cell monolayers; in vivo antibody injection with vascular leakage readout FEBS letters Medium 7589563
1995 TNF-α and IFN-γ induce dose-dependent redistribution of PECAM-1 away from endothelial intercellular junctions without changing total surface PECAM-1 or altering alternatively spliced variants. This redistribution is associated with changes in PECAM-1 cytoskeletal association, suggesting a mechanism by which cytokines regulate leukocyte transmigration. Flow cytometry; immunofluorescence; cytoskeletal fractionation; Northern blot; RT-PCR for splice variants Journal of immunology Medium 7759892
1997 Endothelial tube formation in vitro and in vivo requires both cadherin 5 (VE-cadherin) and CD31 acting in concert to reorganize filamentous actin (F-actin). Neither antibody alone blocked tube formation or F-actin reorganization, but together they did. By immunoprecipitation, a portion of CD31 (as well as cadherin 5) connects to β-catenin, linking it to the F-actin-associated adherens junction complex. In vitro tube formation assay; in vivo wound healing model in SCID mice; anti-CD31 and anti-VE-cadherin blocking antibodies; cytochalasin D treatment; immunoprecipitation of CD31-β-catenin complex Journal of immunology High 9120301
1997 PECAM-1/CD31 functions as an endothelial receptor for Plasmodium falciparum-infected red blood cells (pRBCs). pRBCs bind to PECAM-1/CD31 transfected cells and directly to recombinant PECAM-1/CD31 on plastic. Binding is blocked by soluble PECAM-1/CD31 and by monoclonal antibodies against domains 1–4 of PECAM-1. IFN-γ augments this adhesion. PECAM-1 transfected cell binding assay; recombinant protein binding assay; antibody blocking; IFN-γ stimulation Nature medicine High 9396614
1997 PECAM-1 is involved in angiogenesis: anti-PECAM-1 antibodies blocked in vitro tube formation by rat capillary endothelial cells and cytokine-induced corneal neovascularization in vivo, and prevented vessel growth into bFGF-supplemented subcutaneous gels in mice. In vitro tube formation assay; rat corneal neovascularization model; murine subcutaneous gel implant model; anti-PECAM-1 antibody blocking The American journal of pathology Medium 9284815
1998 Transmigration of growth factor-activated CD34+ hematopoietic progenitor cells (HPCs) across endothelial monolayers is mediated by PECAM-1 (CD31): anti-PECAM-1 monoclonal antibody inhibited transmigration of activated CFCs by ~71%. CD18 also contributed. Activation-induced cell cycle entry was required for transmigration. Transendothelial migration assay; anti-PECAM-1 and anti-CD18 antibody blocking; cell cycle analysis Blood Medium 9454749
1999 VEGF induces β-catenin tyrosine phosphorylation in endothelial cells, and PECAM-1 functions as a reservoir for and modulator of tyrosine-phosphorylated β-catenin at cell junctions. PECAM-1 prevents β-catenin nuclear translocation in transfected SW480 colon carcinoma cells, suggesting PECAM-1 modulates Wnt/β-catenin signaling. Co-immunoprecipitation; Western blot for phospho-β-catenin; transfection of SW480 cells; confocal microscopy Journal of cell science Medium 10462517
1999 PECAM-1/CD31 exists as a dimer (both in solution and on cell membranes) and is heavily N-glycosylated (~21% carbohydrate by mass). Ultracentrifugation showed soluble CD31 equilibrates between monomer and dimer (Kd ~12.5 µM); chemical cross-linking confirmed membrane-expressed CD31 dimerization. Analytical ultracentrifugation; chemical cross-linking of soluble and membrane CD31; mass spectrometry glycan analysis Biochemical and biophysical research communications High 10425179
1999 Homophilic PECAM-1/PECAM-1 interactions on HUVEC support robust endothelial cell adhesion and rescue cells from serum deprivation-induced apoptosis, but do not support cell spreading or migration. αvβ3 integrin is not a PECAM-1 ligand on HUVEC. Tyrosine-phosphorylated PECAM-1 interacts with SHP-2 and at least four other phosphoproteins. Homophilic adhesion assay; apoptosis assay (serum deprivation); cell spreading/migration assay; immunoprecipitation of PECAM-1-SHP-2 complex Journal of cell science Medium 10343075
2000 CD31 cytoplasmic tail signaling activates the small GTPase Rap1 (but not Ras, R-Ras, or Rap2) to induce T cell adhesion via β1 (VLA-4) and β2 (LFA-1) integrins. Activated Rap1 mutant, the Rap1 GEF C3G, and catalytically inactive RapGAP all stimulated T cell adhesion to ICAM and VCAM; negative regulators of Rap1 blocked CD31-dependent adhesion. Rap1 activation assay (GTP-loading); dominant-negative and constitutively active Rap1/RapGEF/RapGAP transfection; T cell adhesion assay to ICAM/VCAM The Journal of cell biology High 10725328
2000 PECAM-1 expression on endothelial cells (not on hematopoietic cells) modulates in vivo bleeding time. PECAM-1-deficient mice had prolonged bleeding times; this was not corrected by engrafting wild-type hematopoietic precursors, but normal bleeding times were seen in wild-type mice reconstituted with PECAM-1-deficient hematopoietic cells. Bone marrow transplantation/chimera experiments; in vivo tail bleeding time assay; PECAM-1 knockout mice The American journal of pathology High 10880378
2002 CD31-mediated homophilic ligation on viable leukocytes promotes active, temperature-dependent detachment from macrophages under low shear (transmitting 'detachment' signals). In apoptotic leukocytes, this CD31-mediated detachment is disabled, promoting tight binding and macrophage engulfment. Thus CD31 switches function upon apoptosis. Flow-based macrophage binding assay; viable vs. apoptotic leukocyte binding; anti-CD31 antibody blocking; temperature-dependence experiments Nature High 12110892
2003 Clustering (multimerization) of PECAM-1 on endothelial cells triggers internalization via a novel endocytic pathway distinct from clathrin- and caveolar-mediated endocytosis. Internalization requires PKC activity, actin rearrangements (sensitive to latrunculin, radicicol, Y27632 [ROCK inhibitor]), and amiloride-sensitive macropinocytosis-like processes. Anti-PECAM-1 conjugate internalization assay; clathrin/caveolin colocalization; pharmacological inhibitors (amiloride, PKC inhibitors, latrunculin, Y27632); dominant-negative dynamin-2 (for ICAM-1 only); actin stress fiber imaging Journal of cell science Medium 12640043
2004 Endothelial cell PECAM-1 expression is protective against endotoxic (LPS-induced) shock. PECAM-1-deficient mice were significantly more sensitive to systemic LPS administration, and bone marrow chimera experiments indicated that the absence of PECAM-1 at endothelial cell-cell junctions (not on hematopoietic cells) accounted for the majority of increased LPS-induced mortality. PECAM-1 knockout mice; LPS challenge model; mortality/pathophysiology readouts; bone marrow chimera experiments American journal of physiology. Heart and circulatory physiology High 15319204
2005 Flow activates ERK1/2 and eNOS via a PECAM1-SHP2-Tie2 signaling pathway. Flow increases tyrosine phosphorylation of both PECAM1 and Tie2 and their association with SHP2. siRNA knockdown of PECAM1 inhibited flow-stimulated Tie2 phosphorylation, ERK1/2, Akt, and eNOS phosphorylation. Thus PECAM1 transactivates Tie2 as an early step in mechanotransduction. Immunoprecipitation/mass spectrometry; PECAM1 and Tie2 siRNA knockdown; phosphorylation assays for ERK1/2, Akt, eNOS, Tie2 The Journal of biological chemistry High 15985432
2006 KSHV K5 ubiquitin ligase removes CD31/PECAM-1 from endothelial cells via a dual mechanism: K5 ubiquitinates pre-existing surface CD31 leading to endocytosis and lysosomal degradation, and newly synthesized CD31 is degraded by proteasomes in the ER (requiring PACS-2 binding to acidic residues in the K5 C-terminus). K5-mediated CD31 loss reduces EC migration. K5 expression in ECs; ubiquitination assay; lysosomal/proteasomal inhibitor treatments; flow cytometry; migration assay; PACS-2 interaction studies Blood High 16601245
2007 PECAM-1 modulates thrombin-induced tissue factor (TF) expression in endothelial cells. PECAM-1 antisense knockdown enhanced TF mRNA/protein induction and nuclear Egr-1 localization after thrombin stimulation. Mechanistically, TF induction proceeds through PAR-1, Gαi/o, Rho kinase, and p38 MAPK activation while PI3K/Akt is dephosphorylated; PECAM-1 presence sustains PI3K/Akt signaling that opposes this pathway. Antisense PECAM-1 knockdown in HUVEC; qRT-PCR/Western blot for TF and Egr-1; PAR-1 antagonist and pertussis toxin pharmacological inhibition; p38 MAPK and PI3K inhibitors; PECAM-1 KO mouse ischemia-reperfusion model Journal of cellular physiology Medium 17111362
2009 PECAM-1 is necessary for flow-induced vascular remodeling. PECAM-1 knockout mice showed impaired inward remodeling and significantly reduced intima-media thickening in response to partial carotid artery ligation. PECAM-1 deficiency reduced NFκB activation, adhesion molecule expression, leukocyte infiltration, Akt activation, and vascular cell proliferation in low-flow conditions. PECAM-1 knockout mice; partial carotid artery ligation model; NFκB and Akt phosphorylation assays; adhesion molecule expression; leukocyte infiltration assessment Arteriosclerosis, thrombosis, and vascular biology High 19390054
2010 TCR stimulation drives cleavage and shedding of extracellular CD31 (domains 1–5) from the T cell surface. The shed CD31 is detectable as a soluble truncated protein in human plasma. Shedding abolishes CD31 inhibitory function because cis-homo-oligomerization (triggered by trans-homophilic engagement of IgD1) cannot occur on CD31-shed cells. A juxta-membrane domain 6 fragment remains on the cell surface and can be targeted by a synthetic CD31 peptide (aa 551–574) to restore ITIM686 and SHP2 phosphorylation and suppress TCR-induced activation in vivo. T cell activation assay; Western blot for shed CD31 in plasma; flow cytometry; phosphorylation assays for ITIM/SHP2; synthetic peptide rescue experiments; in vivo BALB/c mouse immunization model Journal of immunology High 20400708
2010 Cell aggregation in suspension induces tyrosine phosphorylation of PECAM-1 and Pyk2; PECAM-1 and Pyk2 physically interact (shown by co-immunoprecipitation). PECAM-1 lacking exons 11–16 cannot bind Pyk2. siRNA knockdown of both PECAM-1 and Pyk2 reduced cell aggregation and inhibited anchorage-independent tumor cell growth in soft agar, identifying PECAM-1/Pyk2 as mediators of anoikis resistance. Co-immunoprecipitation; domain-deletion mutant of PECAM-1; siRNA knockdown; soft agar colony formation assay; phosphorylation analysis Molecular cancer Medium 20074345
2014 CD31 signals prevent endothelial cell (EC) death induced by TNF-α and cytotoxic T lymphocytes in vitro. Upon TNF receptor engagement, CD31 becomes activated and counteracts the proapoptotic transcriptional program via Erk/Akt pathway activation. Specifically, Akt activation by CD31 prevents FoxO3 nuclear localization, inhibiting transcription of CD95/Fas and caspase 7, and de-repressing cFlar. Both CD31 ITIMs are required for this prosurvival function. In vivo, CD31 gene transfer confers cytoprotection to CD31-negative pancreatic β cells. CD31 knockdown/KO ECs; TNF-α and CTL killing assays; quantitative RT-PCR array; Akt/Erk phosphorylation assays; FoxO3 nuclear localization; ITIM point mutants; in vivo CD31 gene transfer into β cells with allogeneic transplant model Proceedings of the National Academy of Sciences High 26392551
2014 CD31 is a key coinhibitory receptor on dendritic cells (DCs). CD31/SHP-1 signaling during DC maturation reduces NF-κB nuclear translocation, costimulatory molecule expression, and immunogenic cytokines (IL-12, IL-6) while increasing TGF-β and IL-10. Disrupting CD31 signaling promotes immunogenic DC maturation and migration to lymph nodes. CD31-conditioned DCs adoptively transferred in vivo suppressed T cell-mediated autoimmune encephalomyelitis. CD31 signaling manipulation in DCs; NF-κB localization assay; cytokine ELISA; flow cytometry for DC maturation markers; adoptive transfer of CD31-conditioned DCs; EAE mouse model Proceedings of the National Academy of Sciences High 24616502
2015 The crystal structure of PECAM-1 homophilic-binding domain (IgD1 and IgD2) was determined. Both domains exhibit a classical IgSF β-sandwich fold. IgD1 belongs to the I2 set of IgSF folds (not the previously assigned C2 class). Both IgD1 and IgD2 participate in the trans homophilic-binding interface, with a total buried interface area >2300 Ų. This structure provides an atomic-level model of PECAM-1 junction assembly. X-ray crystallography of IgD1-IgD2 fragment Blood High 26702061
2015 PECAM1 specifically mediates flow-induced Gab1 tyrosine phosphorylation and Akt/eNOS activation in endothelial cells. PECAM1 siRNA abolished flow- (but not HGF-) induced Gab1 phosphorylation, membrane translocation, and downstream Akt/eNOS activation. SHP2 is also required for flow-mediated Gab1 phosphorylation. PECAM1 knockout mice showed reduced flow-mediated Gab1 and eNOS phosphorylation in vivo. PECAM1 siRNA in ECs; SHP2 siRNA; PI3K inhibitor; phosphorylation assays; PECAM1 KO mice with voluntary wheel running model Cellular signalling High 26706435
2020 CD31 (PECAM-1) is the specific membrane receptor for Clostridium perfringens β-toxin (CPB) on endothelial cells. CD31 expression corresponds with cell-type specificity of CPB toxicity; ectopic CD31 expression rendered resistant cells and liposomes susceptible to CPB-induced membrane damage. The extracellular Ig6 domain of mouse, human, and porcine CD31 is essential for interaction with CPB. CD31 expression in resistant cell lines; ectopic CD31 expression rendering cells susceptible; liposome reconstitution; Ig-domain deletion mutants; CD31 KO mice; cytotoxicity assays Cell host & microbe High 32497498
2020 CD31 receptor-induced glycolytic reprogramming is required for endothelial barrier (EB) recovery after disruption. Mechanistically, CD31 engagement activates SHP phosphatase, leading to Akt-mediated nuclear exclusion of FoxO1 and β-catenin translocation to the nucleus, collectively driving cMyc transcription and enhanced glycolysis for junction re-annealing. CD31 also sustains mitochondrial respiration but this pathway does not contribute to junction remodeling. Pathologic microvascular leakage in CD31-deficient mice was corrected by pharmacological Akt or AMPK activation. MHC-triggered EC contraction/leakage model; metabolic flux assays; SHP inhibition; Akt/AMPK pharmacological activation; FoxO1 and β-catenin nuclear localization; CD31 KO mice Nature communications High 32681081
2021 PECAM-1 supports leukocyte diapedesis by triggering SHP2 dissociation, which directly dephosphorylates VE-cadherin at Y731, enabling VE-cadherin endocytosis and junctional destabilization. The SHP2-binding site on PECAM-1 is required for VE-cadherin dephosphorylation, and PECAM-1's contribution to diapedesis in vitro and in vivo was strictly dependent on VE-cadherin Y731. Additionally, dephosphorylation requires Ca2+ signaling, non-muscle myosin II, and endothelial cell tension; β-catenin/plakoglobin mask VE-cadherin Y731 until leukocyte docking exerts force on the complex. PECAM-1 SHP2-binding site mutants; VE-cadherin Y731 phosphomutants; in vitro diapedesis assay; in vivo leukocyte extravasation; Ca2+ signaling assays; non-muscle myosin II inhibition; PECAM-1 and VE-cadherin KO/knock-in mice The EMBO journal High 33604918
2023 PECAM1 interacts with PIEZO1 and directs it to endothelial cell-cell junctions. PECAM1's extracellular N-terminus is critical for this interaction, and a C-terminal intracellular domain linked to shear stress also contributes. CDH5 similarly drives PIEZO1 to junctions but unlike PECAM1, its interaction with PIEZO1 is dynamic and increases with shear stress. PIEZO1 does not interact with VEGFR2. PIEZO1 is required for Ca2+-dependent formation of adherens junctions and associated cytoskeleton. Endogenous PIEZO1 tagging in mice; reconstitution studies; high-resolution microscopy; Co-IP; shear stress experiments; PIEZO1 KO functional assays for junction formation Communications biology High 37005489
2023 Physical traction on endothelial PECAM-1 during transendothelial migration (TEM) initiates endothelial signaling (detected by FLIM). Endothelial PECAM-1 acts as part of a mechanotransduction complex with VE-cadherin and VEGFR2. TEM required VEGFR2 and phosphorylation of its Y1175, but not VEGF or VEGFR2 kinase activity. Inducible endothelial-specific VEGFR2 deletion reduced neutrophil extravasation by ≥75% in three mouse inflammation models by selectively blocking diapedesis. Fluorescence lifetime imaging microscopy (FLIM) for traction detection; inducible endothelial-specific VEGFR2 KO mice; VEGFR2 Y1175 phosphomutants; three in vivo mouse inflammation models Immunity High 37643615

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1990 PECAM-1 (CD31) cloning and relation to adhesion molecules of the immunoglobulin gene superfamily. Science (New York, N.Y.) 879 1690453
1991 Molecular and cellular properties of PECAM-1 (endoCAM/CD31): a novel vascular cell-cell adhesion molecule. The Journal of cell biology 644 1874786
1997 Involvement of endothelial PECAM-1/CD31 in angiogenesis. The American journal of pathology 471 9284815
2016 Endothelial functions of platelet/endothelial cell adhesion molecule-1 (CD31). Current opinion in hematology 460 27055047
2007 PECAM-1: a multi-functional molecule in inflammation and vascular biology. Arteriosclerosis, thrombosis, and vascular biology 457 17872453
2000 The small GTPase, Rap1, mediates CD31-induced integrin adhesion. The Journal of cell biology 353 10725328
2002 Apoptosis disables CD31-mediated cell detachment from phagocytes promoting binding and engulfment. Nature 280 12110892
1994 Molecular and functional aspects of PECAM-1/CD31. Immunology today 280 7945775
2014 PECAM-1: regulator of endothelial junctional integrity. Cell and tissue research 270 24435645
2008 Life after the thymus: CD31+ and CD31- human naive CD4+ T-cell subsets. Blood 255 18583570
2003 A novel endocytic pathway induced by clustering endothelial ICAM-1 or PECAM-1. Journal of cell science 254 12640043
1997 PECAM-1/CD31, an endothelial receptor for binding Plasmodium falciparum-infected erythrocytes. Nature medicine 169 9396614
1990 Molecular cloning of CD31, a putative intercellular adhesion molecule closely related to carcinoembryonic antigen. The Journal of experimental medicine 166 2351935
1995 The role of PECAM-1 (CD31) in leukocyte emigration: studies in vitro and in vivo. Journal of leukocyte biology 164 7722409
2010 PECAM-1: conflicts of interest in inflammation. Life sciences 162 20541560
1997 Endothelial cell tube formation depends on cadherin 5 and CD31 interactions with filamentous actin. Journal of immunology (Baltimore, Md. : 1950) 162 9120301
1995 IFN-gamma and TNF-alpha induce redistribution of PECAM-1 (CD31) on human endothelial cells. Journal of immunology (Baltimore, Md. : 1950) 144 7759892
2003 The unfolding tale of PECAM-1. FEBS letters 135 12681475
2001 CD31 expression in intratumoral macrophages: a potential diagnostic pitfall. The American journal of surgical pathology 135 11688576
1994 The role of PECAM-1 in vascular cell biology. Annals of the New York Academy of Sciences 127 8017765
2009 Circulating monocytes expressing CD31: implications for acute and chronic angiogenesis. The American journal of pathology 124 19349357
1995 PECAM-1: its expression and function as a cell adhesion molecule on hemopoietic and endothelial cells. Leukemia & lymphoma 120 8580791
2018 Lung Repair and Regeneration in ARDS: Role of PECAM1 and Wnt Signaling. Chest 115 30392791
1992 Platelet endothelial cell adhesion molecule, PECAM-1, modulates cell migration. Journal of cellular physiology 113 1429859
2013 An immunologist's guide to CD31 function in T-cells. Journal of cell science 110 23761922
1999 PECAM-1 (CD31) functions as a reservoir for and a modulator of tyrosine-phosphorylated beta-catenin. Journal of cell science 100 10462517
2020 CD31 as a Therapeutic Target in Atherosclerosis. Circulation research 98 32324506
2010 Both CD31(+) and CD31⁻ naive CD4(+) T cells are persistent HIV type 1-infected reservoirs in individuals receiving antiretroviral therapy. The Journal of infectious diseases 98 20979453
2004 Endothelial cell PECAM-1 confers protection against endotoxic shock. American journal of physiology. Heart and circulatory physiology 95 15319204
2000 PECAM-1 (CD31) expression modulates bleeding time in vivo. The American journal of pathology 91 10880378
1998 Transmigration of CD34+ cells across specialized and nonspecialized endothelium requires prior activation by growth factors and is mediated by PECAM-1 (CD31). Blood 90 9454749
1992 The cell adhesion molecule CD31 is phosphorylated after cell activation. Down-regulation of CD31 in activated T lymphocytes. The Journal of biological chemistry 89 1544907
2009 PECAM-1 is necessary for flow-induced vascular remodeling. Arteriosclerosis, thrombosis, and vascular biology 87 19390054
2000 Irradiation induced expression of CD31, ICAM-1 and VCAM-1 in human microvascular endothelial cells. Anticancer research 84 11131637
2023 PIEZO1 and PECAM1 interact at cell-cell junctions and partner in endothelial force sensing. Communications biology 78 37005489
2006 Kaposi sarcoma herpesvirus K5 removes CD31/PECAM from endothelial cells. Blood 78 16601245
2015 PECAM-1 isoforms, eNOS and endoglin axis in regulation of angiogenesis. Clinical science (London, England : 1979) 77 25976664
1995 The platelet endothelial cell adhesion molecule-1 (PECAM1) contributes to endothelial barrier function. FEBS letters 75 7589563
1999 Thrombospondin-1, PECAM-1, and regulation of angiogenesis. Histology and histopathology 73 9987673
2019 Mechanotransduction, immunoregulation, and metabolic functions of CD31 in cardiovascular pathophysiology. Cardiovascular research 71 31119265
2006 PECAM-1, a key player in neuroinflammation. European journal of neurology 70 17116209
1999 Homophilic PECAM-1(CD31) interactions prevent endothelial cell apoptosis but do not support cell spreading or migration. Journal of cell science 70 10343075
2015 CD31 signals confer immune privilege to the vascular endothelium. Proceedings of the National Academy of Sciences of the United States of America 68 26392551
2010 TCR stimulation drives cleavage and shedding of the ITIM receptor CD31. Journal of immunology (Baltimore, Md. : 1950) 61 20400708
2014 Vascular channels formed by subpopulations of PECAM1+ melanoma cells. Nature communications 59 25335460
1993 Platelet endothelial cell adhesion molecule (CD31). Current topics in microbiology and immunology 59 8313722
1995 Immunostaining for CD31 and CD34 in Kaposi sarcoma. Journal of clinical pathology 58 8543622
2020 Preservation of microvascular barrier function requires CD31 receptor-induced metabolic reprogramming. Nature communications 57 32681081
2010 VEGF and CD31 association in pituitary adenomas. Endocrine pathology 53 20473646
2005 Flow activates ERK1/2 and endothelial nitric oxide synthase via a pathway involving PECAM1, SHP2, and Tie2. The Journal of biological chemistry 53 15985432
2023 Mesenchymal Stem Cell Aggregation-Released Extracellular Vesicles Induce CD31+ EMCN+ Vessels in Skin Regeneration and Improve Diabetic Wound Healing. Advanced healthcare materials 51 36999744
2016 Endothelial PECAM-1 and its function in vascular physiology and atherogenic pathology. Experimental and molecular pathology 51 27079772
2011 Mesangial cell integrin αvβ8 provides glomerular endothelial cell cytoprotection by sequestering TGF-β and regulating PECAM-1. The American journal of pathology 48 21281793
2021 Coronary stent CD31-mimetic coating favours endothelialization and reduces local inflammation and neointimal development in vivo. European heart journal 47 33580685
2015 Structural basis for PECAM-1 homophilic binding. Blood 47 26702061
2014 CD31 is a key coinhibitory receptor in the development of immunogenic dendritic cells. Proceedings of the National Academy of Sciences of the United States of America 47 24616502
2007 CD31 and CD34 expression as immunohistochemical markers of endothelial transdifferentiation in human cutaneous melanoma. Cellular oncology : the official journal of the International Society for Cellular Oncology 47 17429142
1999 CD31 (PECAM-1) exists as a dimer and is heavily N-glycosylated. Biochemical and biophysical research communications 47 10425179
2020 Ophiopogonin D promotes bone regeneration by stimulating CD31hi EMCNhi vessel formation. Cell proliferation 46 32080957
2023 Mechanotransduction via endothelial adhesion molecule CD31 initiates transmigration and reveals a role for VEGFR2 in diapedesis. Immunity 45 37643615
2021 PECAM-1 supports leukocyte diapedesis by tension-dependent dephosphorylation of VE-cadherin. The EMBO journal 45 33604918
2001 Is PECAM-1 a mechanoresponsive molecule? Cell structure and function 45 11345499
2004 Tumor neoangiogenesis by CD31 and CD105 expression evaluation in breast carcinoma tissue microarrays. Clinical cancer research : an official journal of the American Association for Cancer Research 44 15355911
1996 The human PECAM1 gene maps to 17q23. Genomics 44 8661055
2020 CD31 (PECAM-1) Serves as the Endothelial Cell-Specific Receptor of Clostridium perfringens β-Toxin. Cell host & microbe 43 32497498
2017 CD31 Expression Determines Redox Status and Chemoresistance in Human Angiosarcomas. Clinical cancer research : an official journal of the American Association for Cancer Research 41 29084920
2015 The vascular marker CD31 also highlights histiocytes and histiocyte-like cells within cutaneous tumors. American journal of clinical pathology 41 25596243
2016 Roles of PECAM-1 in cell function and disease progression. European review for medical and pharmacological sciences 40 27775789
1999 Expression of PECAM-1/CD31 isoforms in human brain gliomas. Journal of neuro-oncology 40 10448867
1996 PECAM-1 (CD31) expression in the central nervous system and its role in experimental allergic encephalomyelitis in the rat. Journal of neuroscience research 39 8892086
2018 Double immunofluorescence labeling for CD31 and CD105 as a marker for polyether polyurethane-induced angiogenesis in mice. Histology and histopathology 38 30207375
2010 Cell aggregation induces phosphorylation of PECAM-1 and Pyk2 and promotes tumor cell anchorage-independent growth. Molecular cancer 37 20074345
2012 A CD31-derived peptide prevents angiotensin II-induced atherosclerosis progression and aneurysm formation. Cardiovascular research 36 22293851
2007 Atheroprotective effect of CD31 receptor globulin through enrichment of circulating regulatory T-cells. Journal of the American College of Cardiology 36 17659202
2001 Expression of CD31 by cells of extensive ductal in situ and invasive carcinomas of the breast. The Journal of pathology 35 11400156
2001 CD31 mismatching affects marrow transplantation outcome. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 35 11669217
1992 Cellular and molecular aspects of PECAM-1. Nouvelle revue francaise d'hematologie 35 1340533
2013 Plasmodium falciparum expressing domain cassette 5 type PfEMP1 (DC5-PfEMP1) bind PECAM1. PloS one 34 23874884
2015 Enhanced expression of CD31/platelet endothelial cell adhesion molecule 1 (PECAM1) correlates with hypoxia inducible factor-1 alpha (HIF-1α) in human glioblastoma multiforme. Experimental cell research 33 26376118
2009 CD31+ T cells represent a functionally distinct vascular T cell phenotype. Blood cells, molecules & diseases 33 19897387
2001 Inhibition of antigen-specific T cell trafficking into the central nervous system via blocking PECAM1/CD31 molecule. Journal of neuropathology and experimental neurology 33 11487054
1993 P. Rambotti Lecture. Human naive and memory T cells revisited: new markers (CD31 and CD27) that help define CD4+ T cell subsets. Clinical and experimental rheumatology 31 8394793
2010 Human aging and CD31+ T-cell number, migration, apoptotic susceptibility, and telomere length. Journal of applied physiology (Bethesda, Md. : 1985) 30 20864561
2007 Evaluation of CD31 (PECAM-1) expression using tissue microarray in patients with renal cell carcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 30 17510564
2013 Proangiogenic TIE2(+)/CD31 (+) macrophages are the predominant population of tumor-associated macrophages infiltrating metastatic lymph nodes. Molecules and cells 29 24158612
2010 VE-cadherin and PECAM-1 enhance ALL migration across brain microvascular endothelial cell monolayers. Experimental hematology 29 20470859
2021 Role of aneuploid circulating tumor cells and CD31+ circulating tumor endothelial cells in predicting and monitoring anti-angiogenic therapy efficacy in advanced NSCLC. Molecular oncology 28 34455700
2007 PECAM-1 modulates thrombin-induced tissue factor expression on endothelial cells. Journal of cellular physiology 27 17111362
2011 CD31 is required on CD4+ T cells to promote T cell survival during Salmonella infection. Journal of immunology (Baltimore, Md. : 1950) 26 21734076
2022 Co-expression of ERG and CD31 in a subset of CIC-rearranged sarcoma: a potential diagnostic pitfall. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 24 35440765
2020 Low shear stress induces endothelial cell apoptosis and monocyte adhesion by upregulating PECAM‑1 expression. Molecular medicine reports 24 32323830
2014 Altered CD31 expression and activity in helper T cells of acute coronary syndrome patients. Basic research in cardiology 24 25344833
2014 Preeclampsia does not alter vascular growth and expression of CD31 and vascular endothelial cadherin in human placentas. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 23 25362142
1994 Changes in expression of the cell adhesion molecule PECAM-1 (CD31) during differentiation of human leukemic cell lines. Tissue antigens 23 7878654
2015 PECAM1 regulates flow-mediated Gab1 tyrosine phosphorylation and signaling. Cellular signalling 22 26706435
2022 Comprehensive Immune Profiling Reveals CD56+ Monocytes and CD31+ Endothelial Cells Are Increased in Severe COVID-19 Disease. Journal of immunology (Baltimore, Md. : 1950) 21 34987111
2021 CD31 Mimetic Coating Enhances Flow Diverting Stent Integration into the Arterial Wall Promoting Aneurysm Healing. Stroke 21 33412905
2013 PECAM1(+)/Sca1(+)/CD38(+) vascular cells transform into myofibroblast-like cells in skin wound repair. PloS one 21 23308177
2013 Increased expression of VEGF and CD31 in postradiation rectal tissue: implications for radiation proctitis. Mediators of inflammation 21 23737650
2000 PECAM1, MPO and PRKAR1A at chromosome 17q21-q24 and susceptibility for multiple sclerosis in Sweden and Sardinia. Journal of neuroimmunology 21 10900349

Missed literature

Know a paper Affinage missed for PECAM1? Flag it for the maintainers and the community.

No submissions yet.