Affinage

CAV1

Caveolin-1 · UniProt Q03135

Round 2 corrected
Length
178 aa
Mass
20.5 kDa
Annotated
2026-04-28
130 papers in source corpus 27 papers cited in narrative 27 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Caveolin-1 is an integral membrane scaffolding protein that organizes signaling complexes within caveolae, functioning as a broad negative regulator of receptor tyrosine kinases, Src-family kinases, eNOS, and TGF-β/SMAD signaling through direct interactions mediated by its scaffolding domain (residues 82–101) (PMID:8621645, PMID:8910575, PMID:9325253, PMID:9374534, PMID:11102446). Beyond signal attenuation, CAV1 couples integrins to Fyn–Shc–Ras–ERK signaling to control anchorage-dependent growth, restricts autophagic flux by interacting with the ATG5–ATG12 complex, promotes VEGFR2 ubiquitination and degradation to limit profibrotic VEGF signaling, and marks intraluminal vesicles transported to migrasomes via a Rab10/Myosin Va/RILPL2 axis that delivers CSF-1 during wound healing (PMID:9741627, PMID:32349535, PMID:25237397, PMID:39008679). In stromal fibroblasts, CAV1 regulates p190RhoGAP to control Rho-dependent contractility, extracellular matrix remodeling, and tumor invasion, while its loss in hematopoietic stem cells disrupts quiescence and self-renewal capacity (PMID:21729786, PMID:24675458). CAV1 loss also perturbs retinal energy metabolism and lipid homeostasis, and in the eye elevates intraocular pressure through deregulated eNOS/Akt activity (PMID:33305362, PMID:27228562).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1996 High

    Identification of the caveolin scaffolding domain (residues 82–101) as a direct binding site for H-Ras and Src-family kinases established CAV1 as a scaffolding protein that recruits and negatively regulates signaling molecules within caveolae.

    Evidence GST pull-down with deletion mutants, immune-complex kinase assays, co-immunoprecipitation in 293T cells

    PMID:8621645 PMID:8910575

    Open questions at the time
    • Crystal structure of the caveolin scaffolding domain bound to client kinases has not been solved
    • Stoichiometry of CAV1 oligomers in native caveolae not resolved at atomic level
  2. 1997 High

    Extension of CAV1's inhibitory scaffolding function to eNOS and EGF-R demonstrated it acts as a general kinase/enzyme inhibitor at caveolae, with mutagenesis of cognate binding motifs on both partners confirming direct inhibitory contacts.

    Evidence Purified enzyme inhibition assays, site-directed mutagenesis of eNOS caveolin-binding motif, peptide competition with EGF-R kinase domain

    PMID:9325253 PMID:9374534

    Open questions at the time
    • Whether CAV1 inhibits all caveolin-binding-motif-containing kinases equally in vivo is unresolved
    • Quantitative affinities for different client molecules not systematically measured
  3. 1997 High

    Discovery that CAV1 and CAV2 form stable hetero-oligomeric complexes in caveolae defined the quaternary organization of the caveolin coat.

    Evidence Reciprocal co-immunoprecipitation with mono-specific antibodies, confocal and immunoelectron microscopy

    PMID:9361015

    Open questions at the time
    • Functional consequence of CAV1/CAV2 hetero-oligomerization versus CAV1 homo-oligomerization on signaling regulation not fully dissected
  4. 1998 High

    Linking CAV1 to integrin-mediated signaling (integrin→CAV1→Fyn→Shc→Ras→ERK) revealed it functions not only as a negative regulator but also as a positive membrane adaptor coupling adhesion receptors to growth control.

    Evidence Co-immunoprecipitation, kinase assays, dominant-negative mutants, cell growth assays in CAV1-deficient and reconstituted cells

    PMID:9741627

    Open questions at the time
    • Which integrin α-subunit residues contact CAV1 directly is not mapped
    • Whether CAV1-Fyn coupling operates in all integrin-expressing cell types is not established
  5. 2000 High

    Demonstration that CAV1 scaffolding domain directly binds and suppresses TGF-β type I receptor/SMAD-2 signaling expanded CAV1's inhibitory repertoire to a major morphogen pathway.

    Evidence GST pull-down, co-immunoprecipitation, SMAD-2 phosphorylation and reporter gene assays

    PMID:11102446

    Open questions at the time
    • Whether CAV1 affects TGF-β receptor internalization versus catalytic inhibition specifically is not resolved
  6. 2003 High

    Connecting CAV1 downregulation to E-cadherin endocytosis, β-catenin/TCF transcriptional activation, and epithelial-to-mesenchymal transition established CAV1 as a gatekeeper of epithelial polarity whose loss drives invasion.

    Evidence Antisense knockdown, endocytosis assays, β-catenin/TCF reporter assays, collagen gel invasion in cancer cell lines

    PMID:14706341

    Open questions at the time
    • Direct structural basis for how CAV1 restrains β-catenin signaling independently of GSK-3β is unknown
  7. 2011 High

    Identification of the CAV1→p190RhoGAP→Rho axis in stromal fibroblasts explained how stromal CAV1 promotes ECM stiffening, collagen alignment, and directional tumor cell invasion, resolving the paradox of CAV1 acting as a tumor promoter in the stroma.

    Evidence 3D culture, traction force microscopy, p190RhoGAP activity assays, Cav1-deficient mouse models, human tissue correlation

    PMID:21729786

    Open questions at the time
    • Whether p190RhoGAP is a direct scaffolding-domain client of CAV1 or acts indirectly is not resolved
    • Relative contribution of CAV1-dependent matrix remodeling versus direct tumor-cell CAV1 signaling in metastasis not quantified
  8. 2014 Medium

    Showing that CAV1 promotes VEGFR2 co-localization, ubiquitination, and degradation explained how CAV1 limits profibrotic VEGF/PI3K-Akt/CTGF signaling, with CAV1 silencing phenocopying the systemic sclerosis mesenchymal stem cell phenotype.

    Evidence Co-immunoprecipitation of CAV1/VEGFR2, ubiquitination assays, siRNA knockdown in healthy MSCs, phospho-VEGFR2/Akt measurement

    PMID:25237397

    Open questions at the time
    • Identity of the E3 ubiquitin ligase recruited by CAV1 for VEGFR2 degradation is unknown
    • Whether this mechanism operates in non-mesenchymal cell types is untested
  9. 2014 Medium

    Genetic deletion of Cav-1 revealed it is required for hematopoietic stem cell quiescence; Cav-1−/− HSCs exit quiescence, expand in number, but lose self-renewal and competitive reconstitution capacity.

    Evidence Cav-1−/− mouse, FACS HSC analysis, BrdU cell cycle analysis, competitive transplantation, colony-forming assays

    PMID:24675458

    Open questions at the time
    • Downstream signaling pathway through which CAV1 maintains HSC quiescence (e.g., specific kinase or receptor involved) not identified
    • Whether CAV1-dependent quiescence is cell-autonomous versus niche-dependent is unresolved
  10. 2020 High

    Discovery that CAV1 physically interacts with the ATG5–ATG12 complex and sequesters autophagosome machinery in lipid rafts revealed a direct mechanism by which CAV1 restricts autophagic flux, with in vivo consequences for atheroprotection.

    Evidence Co-immunoprecipitation of CAV1/ATG5-ATG12, lipid raft fractionation, autophagic flux assays, Cav-1−/−Ldlr−/− mouse atherosclerosis model with pharmacological autophagy inhibition

    PMID:32349535

    Open questions at the time
    • Whether CAV1 inhibits ATG5-ATG12 conjugation or merely sequesters the preformed complex is not determined
    • Structural basis of the CAV1–ATG5–ATG12 interaction not characterized
  11. 2024 High

    Identification of CAV1 as a marker of intraluminal vesicles delivered to migrasomes via a Rab10/Myosin Va/RILPL2 motor complex, regulated by LRRK2 phosphorylation, uncovered a novel vesicle trafficking role for CAV1 in CSF-1-dependent monocyte–macrophage differentiation during wound healing.

    Evidence Live-cell imaging, co-immunoprecipitation, siRNA knockdown of Myosin Va/RILPL2/LRRK2, LRRK2 kinase inhibition, wound healing mouse model

    PMID:39008679

    Open questions at the time
    • How CAV1 is sorted into specific ILVs destined for migrasomes versus exosomes is unknown
    • Whether LRRK2-Rab10-CAV1 migrasome transport operates in tissues beyond skin is untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • A unifying structural model explaining how the CAV1 scaffolding domain simultaneously regulates diverse clients (kinases, NOS, ATG complex, Rab10) and how CAV1 switches between signal-inhibitory and vesicle-trafficking roles remains to be established.
  • No high-resolution structure of full-length CAV1 in a lipid bilayer context exists
  • Quantitative selectivity of CAV1 for different clients under physiological conditions is not determined
  • How post-translational modifications (palmitoylation, phosphorylation at Y14) switch CAV1 between its scaffold-inhibitory and trafficking functions is incompletely mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0060090 molecular adaptor activity 4 GO:0005198 structural molecule activity 2 GO:0008289 lipid binding 2
Localization
GO:0005886 plasma membrane 5 GO:0005829 cytosol 1 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-162582 Signal Transduction 10 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-1500931 Cell-Cell communication 2 R-HSA-9612973 Autophagy 2 R-HSA-1474244 Extracellular matrix organization 1 R-HSA-168256 Immune System 1
Partners
CAV2EGFRFYNMYO5ANOS3RAB10SRCTGFBR1
Complex memberships
CAV1/ATG5-ATG12 complexCaveolin-1/Caveolin-2 hetero-oligomer

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 Caveolin-1 (CAV1) co-purifies with Ras in caveolae microdomains and directly interacts with H-Ras via a 41-amino acid membrane-proximal N-terminal domain (residues 82–101), preferentially binding the inactive (GDP-bound) conformation; recombinant caveolin overexpression can recruit non-farnesylated Ras mutants to membranes, demonstrating that CAV1 functions as a scaffolding protein to localize signaling molecules within caveolae. Detergent-free caveolae purification, GST pull-down with deletion mutants, in vitro binding assay, co-immunoprecipitation, overexpression in 293T cells The Journal of biological chemistry High 8621645
1996 The caveolin scaffolding domain (residues 82–101) of CAV1 directly binds wild-type c-Src (but not constitutively active v-Src) and functionally suppresses Src auto-activation; in co-transfection experiments, full-length caveolin dramatically reduces c-Src tyrosine kinase activity. The same domain also interacts with Gα subunits and H-Ras, establishing CAV1 as a shared scaffolding/negative-regulatory platform for multiple signaling molecules. GST pull-down with CAV1 deletion mutants, immune-complex kinase assay, co-transfection in 293T cells, recombinant peptide inhibition of purified Src The Journal of biological chemistry High 8910575
1997 CAV1 directly binds endothelial nitric oxide synthase (eNOS) through the caveolin scaffolding domain (residues 61–101) and inhibits eNOS, iNOS, and nNOS enzymatic activity; site-directed mutagenesis of the predicted caveolin-binding motif within eNOS (residues 310–570) blocks caveolin-1-mediated suppression of NO release in co-transfection experiments, establishing CAV1 as a direct inhibitor/chaperone of NOS enzymes. GST pull-down with caveolin-1 deletion mutants, peptide inhibition assays with purified NOS enzymes, site-directed mutagenesis of eNOS, co-transfection NO release assay The Journal of biological chemistry High 9325253
1997 CAV1 directly interacts with the EGF receptor (EGF-R) via a conserved caveolin-binding motif within the kinase domain (region IX), and the caveolin scaffolding domains of caveolin-1 and caveolin-3 inhibit EGF-R autophosphorylation in vitro; similar inhibition occurs for protein kinase C, suggesting CAV1 acts as a general kinase inhibitor. In vitro binding assay (caveolin scaffolding domain peptides vs. purified EGF-R kinase), autophosphorylation assay, peptide competition The Journal of biological chemistry High 9374534
1997 Caveolin-1 and caveolin-2 are strictly co-localized in caveolae membranes and form a stable hetero-oligomeric complex in vivo, as demonstrated by co-immunoprecipitation with mono-specific antibodies and dual-label confocal immunofluorescence; their expression levels can be regulated independently. Co-immunoprecipitation with mono-specific monoclonal antibodies, confocal immunofluorescence, immunoelectron microscopy The Journal of biological chemistry High 9361015
1998 CAV1 functions as a membrane adaptor linking integrin α subunits to the Src-family kinase Fyn; upon integrin ligation, Fyn is activated, binds Shc via its SH3 domain, and triggers tyrosine phosphorylation of Shc at Y317, coupling integrins to the Ras-ERK pathway and anchorage-dependent cell growth. Co-immunoprecipitation, kinase assays, dominant-negative expression, cell growth assays in CAV1-deficient and reconstituted cells Cell High 9741627
2000 CAV1 directly interacts with the Type I TGF-β receptor via its scaffolding domain and suppresses TGF-β-mediated SMAD-2 phosphorylation and downstream signaling; this interaction places CAV1 as a negative regulator of TGF-β/SMAD signaling at the plasma membrane. Co-immunoprecipitation, GST pull-down with caveolin-1 scaffolding domain, SMAD-2 phosphorylation assays, reporter gene assays The Journal of biological chemistry High 11102446
2000 PrPc (cellular prion protein) signals through a caveolin-1-dependent coupling to Fyn tyrosine kinase in differentiated neuronal cells; antibody-mediated cross-linking of PrPc activates Fyn in a caveolin-1-dependent manner restricted to neurites of serotonergic/noradrenergic progenies. Antibody-mediated PrPc cross-linking, Fyn kinase activity assays, 1C11 neuronal differentiation model, co-immunoprecipitation Science Medium 10988071
2003 EGF treatment induces caveolin-1-dependent endocytosis of E-cadherin; chronic EGF signaling transcriptionally downregulates caveolin-1 and induces Snail, leading to loss of E-cadherin expression. CAV1 downregulation also enhances β-catenin-TCF/LEF-1 transcriptional activity in a GSK-3β-independent manner, promoting epithelial-to-mesenchymal transition and tumor cell invasion. Antisense RNA-mediated CAV1 knockdown, co-immunoprecipitation, immunofluorescence endocytosis assays, reporter gene assay (β-catenin-TCF/LEF-1), collagen gel invasion assay Cancer cell High 14706341
2006 CAV1 is a direct transcriptional target of EWS/FLI-1 in Ewing's sarcoma (ESFT); CAV1 knockdown upregulates Snail and causes loss of E-cadherin, inhibiting anchorage-independent growth and reducing tumor xenograft growth. Re-expression of CAV1 or E-cadherin rescues the oncogenic phenotype, establishing a CAV1/Snail/E-cadherin pathway as central to EWS/FLI-1-driven oncogenesis. Antisense and shRNA knockdown, chromatin immunoprecipitation, microarray analysis, anchorage-independent growth assay, nude mouse xenograft, re-expression rescue experiments Cancer research High 17047056
2007 Cav-1 knockout mice exhibit organ-specific stromal growth disorders (in tissues with normally high cav-1 expression) and secondary epithelial growth/differentiation abnormalities in adjacent cells that normally express low cav-1; this indicates cav-1 loss in stroma indirectly disrupts epithelial homeostasis via paracrine mechanisms. Genetic knockout mouse model (cav-1-/-, exon 2 null mutation), histopathological analysis, long-term phenotypic monitoring Experimental and molecular pathology Medium 18358473
2011 Stromal caveolin-1 (Cav1) promotes tumor invasion and metastasis by regulating p190RhoGAP activity, thereby enhancing Rho-dependent cell contractility, force generation, collagen fiber alignment, and extracellular matrix stiffening; Cav1-expressing carcinoma-associated fibroblasts (CAFs) remodel the peri- and intra-tumoral microenvironment to facilitate directional tumor cell migration, correlating with increased metastatic potency in vivo. 3D culture systems, traction force microscopy, collagen gel contraction assays, p190RhoGAP interaction/activity assays, Cav1-deficient mouse models, in vivo tumor implantation, human carcinoma tissue analysis Cell High 21729786
2011 Cav-1 and FASN physically interact in melanoma cells; in diet-induced obese mice with elevated melanoma progression, both Cav-1 and FASN are coordinately upregulated in tumors, and enhanced Cav-1/FASN/pAkt signaling controls melanoma cell proliferation. Co-immunoprecipitation (Cav-1/FASN interaction), Western blot, in vivo high-fat diet mouse model, cell proliferation assays International journal of cancer Medium 21387314
2013 Caveolin-1 (CAV1) negatively regulates exosome uptake via lipid raft-dependent endocytosis; CAV1 suppresses ERK1/2-HSP27 signaling that is required for glioblastoma exosome internalization, establishing CAV1 as a negative regulator of exosomal cargo uptake. siRNA knockdown of CAV1, ERK1/2 phosphorylation assays, lipid raft disruption, live-cell imaging of exosome uptake, HSP27 knockdown The Journal of biological chemistry Medium 23653359
2014 Reduced Cav-1 expression in systemic sclerosis (SSc) mesenchymal stem cells impairs Cav-1/VEGFR2 co-localization and VEGFR2 ubiquitination/degradation, leading to increased VEGFR2 tyrosine phosphorylation, PI3K-Akt pathway activation, and elevated CTGF expression; CAV1 silencing in healthy MSCs recapitulates the SSc profibrotic phenotype, demonstrating that CAV1 normally promotes VEGFR2 degradation to limit profibrotic VEGF signaling. Immunofluorescence, co-immunoprecipitation (Cav-1/VEGFR2), ubiquitination assays, Western blot (pVEGFR2, pAkt), siRNA knockdown of CAV1, CTGF expression analysis Fibrogenesis & tissue repair Medium 25237397
2015 IFITM1 promotes colorectal cancer cell invasion through CAV1 as a downstream target; knockdown of CAV1 abrogates the inhibitory effect of IFITM1 siRNA on cell invasion, placing CAV1 downstream of IFITM1 in a pro-invasive signaling axis in CRC cells. siRNA knockdown of IFITM1 and CAV1, Transwell migration/invasion assays, Western blot, patient cohort expression analysis Cancer letters Low 26259513
2016 CAV1 knockout mice have elevated intraocular pressure and reduced conventional aqueous outflow facility; despite CAV1 loss, eNOS activity is paradoxically increased (elevated eNOS-phospho Ser1177, Akt, Akt-phospho Ser473) while eNOS-phospho Thr495 is reduced; increased tyrosine nitration of proteins including protein kinase G is proposed as the mechanism for pressure elevation, indicating CAV1 normally restrains eNOS activity in the conventional outflow pathway of the eye. CAV1 KO mouse model, rebound tonometry (IOP measurement), Western blot (eNOS phosphorylation sites, Akt), perfusion outflow facility measurement, topical NO donor/NOS inhibitor pharmacology Investigative ophthalmology & visual science Medium 27228562
2018 Palmitic acid (PA)-induced autophagy in hippocampal astrocytes leads to autophagic degradation of Cav-1; this Cav-1 degradation is necessary and sufficient for PA-induced apoptosis and inflammation, as Cav-1 loss activates apoptotic and inflammatory pathways; chronic high-fat diet also reduces Cav-1 in hippocampal astrocytes in vivo. Primary astrocyte cultures, PA treatment, autophagy inhibitors/inducers, Cav-1 siRNA knockdown, apoptosis assays (Annexin V, caspase), inflammatory cytokine measurement, in vivo high-fat diet rat model Cell death & disease Medium 29991726
2019 Caveolin-1 (Cav-1) directly binds TLR4 in the spinal cord and promotes TLR4 expression; in diabetic neuropathic pain, Cav-1 is upregulated, and pharmacological inhibition of Cav-1 with daidzein reduces TLR4 expression and subsequent phosphorylation of NR2B (NMDA receptor subunit 2B), ameliorating pain hypersensitivity. Streptozocin diabetes rat model, Western blot, immunofluorescence, subcutaneous Cav-1 inhibitor (daidzein) administration, pain behavioral tests (mechanical withdrawal threshold, thermal withdrawal latency) Journal of cellular physiology Low 31318049
2020 CAV1 deficiency in aortic endothelium increases autophagic flux by enhancing autophagosome formation; mechanistically, CAV1 interacts with the ATG5-ATG12 autophagy complex and controls the localization of autophagosome components in lipid rafts, thereby restricting autophagy; pharmacological inhibition of autophagy in Cav-1-/- mice attenuates their atheroprotection by restoring endothelial inflammation and macrophage recruitment. Ldlr-/- and Cav-1-/-Ldlr-/- mouse models on Western diet, autophagic flux assays, co-immunoprecipitation (CAV1/ATG5-ATG12), lipid raft fractionation, autophagy inhibitor treatment, en face atherosclerosis quantification, inflammation markers Arteriosclerosis, thrombosis, and vascular biology High 32349535
2021 WTAP-mediated m6A methylation at the 3'-UTR of CAV-1 mRNA reduces CAV-1 protein expression in endometrial cancer; reduced CAV-1 de-represses NF-κB signaling, promoting cancer progression; RNA immunoprecipitation confirmed enrichment of m6A and METTL3 at the CAV-1 3'-UTR, and WTAP knockdown upregulates CAV-1 and inhibits NF-κB. siRNA knockdown of WTAP, RT-qPCR, Western blot, RNA immunoprecipitation-qPCR (m6A and METTL3 enrichment on CAV-1 3'-UTR), cell proliferation/migration/invasion assays, in vivo tumor model Cell biology international Medium 33559954
2022 CD26 promotes colorectal cancer angiogenesis and metastasis partly through CAV1; CAV1 overexpression abrogates CD26-induced MMP1 upregulation, placing CAV1 as a negative regulator of the CD26→MMP1 pro-invasive axis in CRC. CD26 overexpression/knockdown, CAV1 overexpression, genome-wide mRNA array, qPCR, wound healing, migration/invasion assays, in vivo mouse models International journal of molecular sciences Low 35163100
2023 Breast cancer-derived exosomes transport Cav-1 to the pre-metastatic niche in the lung; exosomal Cav-1 acts as an intercellular signaling molecule that regulates PMN marker gene expression in lung epithelial cells, promotes tenascin-C secretion by lung fibroblasts causing ECM deposition, and inhibits the PTEN/CCL2/VEGF-A pathway in macrophages to facilitate M2 polarization and angiogenesis. Differential ultracentrifugation, nanoparticle tracking analysis, transmission electron microscopy, Transwell assays, mammary tumor mouse models, Western blot, flow cytometry, RT-qPCR, immunofluorescence, gene overexpression and siRNA knockdown Theranostics Medium 37056561
2023 miR-199a-5p directly targets and inhibits Cav-1 mRNA; miR-199a-5p overexpression enhances neuronal differentiation of neural stem cells and promotes neurogenesis after ischemic stroke in vivo; Cav-1 siRNA phenocopies miR-199a-5p overexpression effects on NSC differentiation, and Cav-1 inhibition correlates with increased VEGF and BDNF. Dual-luciferase reporter assay (confirming Cav-1 as direct miR-199a-5p target), NSC transfection, immunofluorescence, Western blot, intracerebroventricular miRNA agomir/antagomir injection in stroke rats, infarct volume measurement CNS neuroscience & therapeutics Medium 37349971
2024 CAV1 marks intraluminal vesicles (ILVs) destined for migrasomes; Rab10-CAV1 vesicle transport to migrasomes requires the motor protein Myosin Va and adaptor proteins RILPL2; LRRK2-mediated phosphorylation of Rab10 regulates this transport process; CSF-1 is transported to migrasomes via this Rab10-CAV1 mechanism, promoting monocyte-macrophage differentiation during skin wound healing. Live-cell fluorescence imaging, co-immunoprecipitation, siRNA knockdown of Myosin Va/RILPL2/LRRK2, LRRK2 kinase inhibition, wound healing mouse model, monocyte-macrophage differentiation assays Proceedings of the National Academy of Sciences of the United States of America High 39008679
2014 Cav-1 deletion impairs hematopoietic stem cell (HSC) quiescence, promoting cell cycle progression through G2/M phase; Cav-1-/- mice show increased HSC numbers but reduced self-renewal capacity (colony assay) and failure to reconstitute hematopoiesis in competitive transplantation, indicating CAV1 is required for maintaining HSC quiescence and function. Cav-1-/- mouse model, FACS analysis of HSC subpopulations, in vitro clonogenic assay, in vivo competitive transplantation, cell cycle analysis (BrdU incorporation) Cell death & disease Medium 24675458
2020 Cav-1 deficiency in retinal cells causes dysregulation of oxidative lipidomics and reduced energy production (decreased Na+/K+-ATPase, oxidative phosphorylation CII, cytochrome c, and oxygen consumption rate), resulting in retinal function deficits; decreased Sirt1 accompanies these changes; oral nicotinamide increases Sirt1, restores energy metabolism, and improves retinal function in Cav-1-/- mice. Cav-1-/- mouse model, oxidative lipidomics (oxylipin profiling), Seahorse energy flux assay (OCR measurement), electroretinogram, Western blot (Sirt1, cytochrome c, Na+/K+-ATPase), nicotinamide oral supplementation Journal of neurochemistry Medium 33305362

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2004 Immunoaffinity profiling of tyrosine phosphorylation in cancer cells. Nature biotechnology 916 15592455
1996 Co-purification and direct interaction of Ras with caveolin, an integral membrane protein of caveolae microdomains. Detergent-free purification of caveolae microdomains. The Journal of biological chemistry 916 8621645
1998 Dynamic activation of endothelial nitric oxide synthase by Hsp90. Nature 837 9580552
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2000 DNA cloning using in vitro site-specific recombination. Genome research 815 11076863
2009 High levels of exosomes expressing CD63 and caveolin-1 in plasma of melanoma patients. PloS one 756 19381331
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2006 Phosphoinositide-mediated adaptor recruitment controls Toll-like receptor signaling. Cell 699 16751103
2012 A census of human soluble protein complexes. Cell 689 22939629
1996 Src tyrosine kinases, Galpha subunits, and H-Ras share a common membrane-anchored scaffolding protein, caveolin. Caveolin binding negatively regulates the auto-activation of Src tyrosine kinases. The Journal of biological chemistry 684 8910575
1997 Dissecting the interaction between nitric oxide synthase (NOS) and caveolin. Functional significance of the nos caveolin binding domain in vivo. The Journal of biological chemistry 679 9325253
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2000 Signal transduction through prion protein. Science (New York, N.Y.) 626 10988071
1998 A requirement for caveolin-1 and associated kinase Fyn in integrin signaling and anchorage-dependent cell growth. Cell 590 9741627
2011 Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors tumor invasion and metastasis. Cell 586 21729786
2018 High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies. Molecular cell 580 29395067
2013 Exosome uptake depends on ERK1/2-heat shock protein 27 signaling and lipid Raft-mediated endocytosis negatively regulated by caveolin-1. The Journal of biological chemistry 569 23653359
1997 Interaction of a receptor tyrosine kinase, EGF-R, with caveolins. Caveolin binding negatively regulates tyrosine and serine/threonine kinase activities. The Journal of biological chemistry 569 9374534
2003 Downregulation of caveolin-1 function by EGF leads to the loss of E-cadherin, increased transcriptional activity of beta-catenin, and enhanced tumor cell invasion. Cancer cell 552 14706341
2021 Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature 532 33845483
2000 Caveolin-1 regulates transforming growth factor (TGF)-beta/SMAD signaling through an interaction with the TGF-beta type I receptor. The Journal of biological chemistry 494 11102446
2012 Meta-analysis identifies six new susceptibility loci for atrial fibrillation. Nature genetics 490 22544366
2011 Analysis of the myosin-II-responsive focal adhesion proteome reveals a role for β-Pix in negative regulation of focal adhesion maturation. Nature cell biology 490 21423176
1997 Cell-type and tissue-specific expression of caveolin-2. Caveolins 1 and 2 co-localize and form a stable hetero-oligomeric complex in vivo. The Journal of biological chemistry 474 9361015
2003 Functional role of L-type Cav1.3 Ca2+ channels in cardiac pacemaker activity. Proceedings of the National Academy of Sciences of the United States of America 367 12700358
2005 Role of hippocampal Cav1.2 Ca2+ channels in NMDA receptor-independent synaptic plasticity and spatial memory. The Journal of neuroscience : the official journal of the Society for Neuroscience 355 16251435
2014 L-type CaV1.2 calcium channels: from in vitro findings to in vivo function. Physiological reviews 283 24382889
2004 Essential role of Ca2+-binding protein 4, a Cav1.4 channel regulator, in photoreceptor synaptic function. Nature neuroscience 245 15452577
2011 BIN1 is reduced and Cav1.2 trafficking is impaired in human failing cardiomyocytes. Heart rhythm 134 22138472
2006 Caveolin-1 (CAV1) is a target of EWS/FLI-1 and a key determinant of the oncogenic phenotype and tumorigenicity of Ewing's sarcoma cells. Cancer research 123 17047056
2005 Association of CaV1.3 L-type calcium channels with Shank. The Journal of neuroscience : the official journal of the Society for Neuroscience 123 15689539
2010 CaV1.2 beta-subunit coordinates CaMKII-triggered cardiomyocyte death and afterdepolarizations. Proceedings of the National Academy of Sciences of the United States of America 106 20194790
2005 Splicing for alternative structures of Cav1.2 Ca2+ channels in cardiac and smooth muscles. Cardiovascular research 100 16051206
2004 Ser1928 is a common site for Cav1.2 phosphorylation by protein kinase C isoforms. The Journal of biological chemistry 100 15509562
2009 Elementary properties of CaV1.3 Ca(2+) channels expressed in mouse cochlear inner hair cells. The Journal of physiology 97 19917569
2007 Ca2+-binding proteins tune Ca2+-feedback to Cav1.3 channels in mouse auditory hair cells. The Journal of physiology 96 17947313
2001 Uptake, effects, and metabolism of cyanobacterial toxins in the emergent reed plant Phragmites australis (cav.) trin. ex steud. Environmental toxicology and chemistry 96 11345462
2020 Cav-1 (Caveolin-1) Deficiency Increases Autophagy in the Endothelium and Attenuates Vascular Inflammation and Atherosclerosis. Arteriosclerosis, thrombosis, and vascular biology 94 32349535
2023 Tumor-derived Cav-1 promotes pre-metastatic niche formation and lung metastasis in breast cancer. Theranostics 93 37056561
2012 Presynaptic CaV1.3 channels regulate synaptic ribbon size and are required for synaptic maintenance in sensory hair cells. The Journal of neuroscience : the official journal of the Society for Neuroscience 91 23197719
2004 An essential role of Cav1.2 L-type calcium channel for urinary bladder function. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 88 15132976
2010 Progress in the structural understanding of voltage-gated calcium channel (CaV) function and modulation. Channels (Austin, Tex.) 86 21139419
2011 Diet-induced obesity increases melanoma progression: involvement of Cav-1 and FASN. International journal of cancer 79 21387314
2009 CaV1.2 channelopathies: from arrhythmias to autism, bipolar disorder, and immunodeficiency. Pflugers Archiv : European journal of physiology 77 19916019
2011 Functional characterization of alternative splicing in the C terminus of L-type CaV1.3 channels. The Journal of biological chemistry 76 21998309
2015 IFITM1 promotes the metastasis of human colorectal cancer via CAV-1. Cancer letters 69 26259513
2018 A review of the role of cav-1 in neuropathology and neural recovery after ischemic stroke. Journal of neuroinflammation 68 30572925
2014 Basal and β-adrenergic regulation of the cardiac calcium channel CaV1.2 requires phosphorylation of serine 1700. Proceedings of the National Academy of Sciences of the United States of America 66 25368181
2009 Developmental control of CaV1.2 L-type calcium channel splicing by Fox proteins. Molecular and cellular biology 66 19564422
2016 Phosphorylation of Cav1.2 on S1928 uncouples the L-type Ca2+ channel from the β2 adrenergic receptor. The EMBO journal 60 27103070
2012 Exploring the dominant role of Cav1 channels in signalling to the nucleus. Bioscience reports 60 23088728
2003 Enhanced expression of L-type Cav1.3 calcium channels in murine embryonic hearts from Cav1.2-deficient mice. The Journal of biological chemistry 55 12900400
2019 TDP-43 regulates early-phase insulin secretion via CaV1.2-mediated exocytosis in islets. The Journal of clinical investigation 52 31355778
2014 Characterization of Cav1.4 complexes (α11.4, β2, and α2δ4) in HEK293T cells and in the retina. The Journal of biological chemistry 52 25468907
2011 Surface traffic of dendritic CaV1.2 calcium channels in hippocampal neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 52 21940459
2009 PIKfyve regulates CaV1.2 degradation and prevents excitotoxic cell death. The Journal of cell biology 52 19841139
2010 Homeostatic switch in hebbian plasticity and fear learning after sustained loss of Cav1.2 calcium channels. The Journal of neuroscience : the official journal of the Society for Neuroscience 51 20573883
2018 The autophagic degradation of Cav-1 contributes to PA-induced apoptosis and inflammation of astrocytes. Cell death & disease 49 29991726
2015 RIM1/2-Mediated Facilitation of Cav1.4 Channel Opening Is Required for Ca2+-Stimulated Release in Mouse Rod Photoreceptors. The Journal of neuroscience : the official journal of the Society for Neuroscience 46 26400943
2012 CaV1.2 sparklets in heart and vascular smooth muscle. Journal of molecular and cellular cardiology 46 23220157
2008 Stable membrane expression of postsynaptic CaV1.2 calcium channel clusters is independent of interactions with AKAP79/150 and PDZ proteins. The Journal of neuroscience : the official journal of the Society for Neuroscience 46 19091974
2017 Genomic upregulation of cardiac Cav1.2α and NCX1 by estrogen in women. Biology of sex differences 43 28807015
2010 Analysis of Cav1.2 and ryanodine receptor clusters in rat ventricular myocytes. Biophysical journal 43 21156134
2022 CD26 Induces Colorectal Cancer Angiogenesis and Metastasis through CAV1/MMP1 Signaling. International journal of molecular sciences 42 35163100
2021 WTAP facilitates progression of endometrial cancer via CAV-1/NF-κB axis. Cell biology international 42 33559954
2020 Disruption of Cav1.2-mediated signaling is a pathway for ketamine-induced pathology. Nature communications 42 32859919
2015 Cell-type-specific tuning of Cav1.3 Ca(2+)-channels by a C-terminal automodulatory domain. Frontiers in cellular neuroscience 42 26379493
2002 Sequence analysis of the full-length cloned DNA of a chicken anaemia virus (CAV) strain from Bangladesh: evidence for genetic grouping of CAV strains based on the deduced VP1 amino acid sequences. Journal of veterinary medicine. B, Infectious diseases and veterinary public health 42 12420868
2015 Ca(2+) permeation and/or binding to CaV1.1 fine-tunes skeletal muscle Ca(2+) signaling to sustain muscle function. Skeletal muscle 40 25717360
2018 Cav-1 (Caveolin-1) and Arterial Remodeling in Adult Moyamoya Disease. Stroke 38 30355208
2016 Orai1 and TRPC1 Proteins Co-localize with CaV1.2 Channels to Form a Signal Complex in Vascular Smooth Muscle Cells. The Journal of biological chemistry 38 27535226
2015 Cav1.3 Channels as Key Regulators of Neuron-Like Firings and Catecholamine Release in Chromaffin Cells. Current molecular pharmacology 38 25966692
2013 Mosaic synaptopathy and functional defects in Cav1.4 heterozygous mice and human carriers of CSNB2. Human molecular genetics 38 24163243
2010 Expression and roles of Cav1.3 (α1D) L-type Ca²+ channel in atrioventricular node automaticity. Journal of molecular and cellular cardiology 35 20951705
2017 Ca2+ protein alpha 1D of CaV1.3 regulates intracellular calcium concentration and migration of colon cancer cells through a non-canonical activity. Scientific reports 34 29079724
2016 eNOS Activity in CAV1 Knockout Mouse Eyes. Investigative ophthalmology & visual science 34 27228562
2005 Cav1.4 encodes a calcium channel with low open probability and unitary conductance. Biophysical journal 34 16085774
2020 Kirenol inhibits RANKL-induced osteoclastogenesis and prevents ovariectomized-induced osteoporosis via suppressing the Ca2+-NFATc1 and Cav-1 signaling pathways. Phytomedicine : international journal of phytotherapy and phytopharmacology 33 33126167
2013 Protein kinase C-dependent activation of CaV1.2 channels selectively controls human TH2-lymphocyte functions. The Journal of allergy and clinical immunology 33 24365142
2020 Synaptic ribbons foster active zone stability and illumination-dependent active zone enrichment of RIM2 and Cav1.4 in photoreceptor synapses. Scientific reports 32 32249787
2016 Regulation of aldosterone secretion by Cav1.3. Scientific reports 32 27098837
2017 Cav-1 promote lung cancer cell proliferation and invasion through lncRNA HOTAIR. Gene 31 29080835
2008 Expression of calcium channel CaV1.3 in cat spinal cord: light and electron microscopic immunohistochemical study. The Journal of comparative neurology 30 18095323
2024 Key Roles of CACNA1C/Cav1.2 and CALB1/Calbindin in Prefrontal Neurons Altered in Cognitive Disorders. JAMA psychiatry 29 38776078
2015 Homer proteins mediate the interaction between STIM1 and Cav1.2 channels. Biochimica et biophysica acta 29 25712868
2007 Regulation of Cav1.2 current: interaction with intracellular molecules. Journal of pharmacological sciences 29 17409629
2016 Tagetes lucida Cav.: Ethnobotany, phytochemistry and pharmacology of its tranquilizing properties. Journal of ethnopharmacology 28 26873624
2010 Spatial association of the Cav1.2 calcium channel with α5β1-integrin. American journal of physiology. Cell physiology 28 21178109
2007 Mice with cav-1 gene disruption have benign stromal lesions and compromised epithelial differentiation. Experimental and molecular pathology 28 18358473
2019 Genetic silencing of striatal CaV1.3 prevents and ameliorates levodopa dyskinesia. Movement disorders : official journal of the Movement Disorder Society 27 31002755
2019 Cav-1 participates in the development of diabetic neuropathy pain through the TLR4 signaling pathway. Journal of cellular physiology 26 31318049
2015 Cacna1c (Cav1.2) Modulates Electroencephalographic Rhythm and Rapid Eye Movement Sleep Recovery. Sleep 26 25845695
2014 Impaired Cav-1 expression in SSc mesenchymal cells upregulates VEGF signaling: a link between vascular involvement and fibrosis. Fibrogenesis & tissue repair 26 25237397
2024 Rab10-CAV1 mediated intraluminal vesicle transport to migrasomes. Proceedings of the National Academy of Sciences of the United States of America 25 39008679
2014 Cav-1 deletion impaired hematopoietic stem cell function. Cell death & disease 25 24675458
2018 Tissue-selective restriction of RNA editing of CaV1.3 by splicing factor SRSF9. Nucleic acids research 24 29733375
2012 Structural determinants of CaV1.3 L-type calcium channel gating. Channels (Austin, Tex.) 24 22760075
2016 Protein kinase A modulation of CaV1.4 calcium channels. Nature communications 23 27456671
2006 Protein kinase C activation inhibits Cav1.3 calcium channel at NH2-terminal serine 81 phosphorylation site. American journal of physiology. Heart and circulatory physiology 23 16973824
2021 Cav1.4 dysfunction and congenital stationary night blindness type 2. Pflugers Archiv : European journal of physiology 20 34212239
2016 Rescuing cardiac automaticity in L-type Cav1.3 channelopathies and beyond. The Journal of physiology 20 27374078
2015 Modulation of CaV1.2 calcium channel by neuropeptide W regulates vascular myogenic tone via G protein-coupled receptor 7. Journal of hypertension 20 26536090
2023 ANO1, CaV1.2, and IP3R form a localized unit of EC-coupling in mouse pulmonary arterial smooth muscle. The Journal of general physiology 19 37702787
2022 Bipolar-associated miR-499-5p controls neuroplasticity by downregulating the Cav1.2 subunit CACNB2. EMBO reports 19 35969184
2020 AXL and CAV-1 play a role for MTH1 inhibitor TH1579 sensitivity in cutaneous malignant melanoma. Cell death and differentiation 19 31919461
2015 L-type Calcium Channel Cav1.2 Is Required for Maintenance of Auditory Brainstem Nuclei. The Journal of biological chemistry 19 26242732
2012 Phenolic compound production in relation to differentiation in cell and tissue cultures of Larrea divaricata (Cav.). Plant science : an international journal of experimental plant biology 19 22794913
2011 Perinatal and postnatal expression of Cav1.3 α1D Ca²⁺ channel in the rat heart. Pediatric research 18 21378599
2003 The influence of the Miocene Mediterranean desiccation on the geographical expansion and genetic variation of Androcymbium gramineum (Cav.) McBride (Colchicaceae). Molecular ecology 18 12755880
2023 MiR-199a-5p enhances neuronal differentiation of neural stem cells and promotes neurogenesis by targeting Cav-1 after cerebral ischemia. CNS neuroscience & therapeutics 17 37349971
2023 The human channel gating-modifying A749G CACNA1D (Cav1.3) variant induces a neurodevelopmental syndrome-like phenotype in mice. JCI insight 17 37698939
2022 Antenatal Dexamethasone Exposure Impairs Vascular Contractile Functions via Upregulating IP3 Receptor 1 and Cav1.2 in Adult Male Offspring. Hypertension (Dallas, Tex. : 1979) 17 35762340
2016 Resistance to pathologic cardiac hypertrophy and reduced expression of CaV1.2 in Trpc3-depleted mice. Molecular and cellular biochemistry 17 27522668
2015 Decalmodulation of Cav1 channels by CaBPs. Channels (Austin, Tex.) 17 26155893
2009 Silencing of Cav1.2 gene in neonatal cardiomyocytes by lentiviral delivered shRNA. Biochemical and biophysical research communications 17 19422800
2024 CardioDPi: An explainable deep-learning model for identifying cardiotoxic chemicals targeting hERG, Cav1.2, and Nav1.5 channels. Journal of hazardous materials 16 38805819
2022 Huntington-associated protein 1 inhibition contributes to neuropathic pain by suppressing Cav1.2 activity and attenuating inflammation. Pain 16 36508175
2021 Gating pore currents occur in CaV1.1 domain III mutants associated with HypoPP. The Journal of general physiology 16 34463712
2019 RBP2 stabilizes slow Cav1.3 Ca2+ channel inactivation properties of cochlear inner hair cells. Pflugers Archiv : European journal of physiology 16 31848688
2012 The interrelationships between Src, Cav-1 and RhoGD12 in transitional cell carcinoma of the bladder. British journal of cancer 16 22353809
2020 Nicotinamide ameliorates energy deficiency and improves retinal function in Cav-1-/- mice. Journal of neurochemistry 15 33305362
2019 Dysfunctional Cav1.2 channel in Timothy syndrome, from cell to bedside. Experimental biology and medicine (Maywood, N.J.) 15 31324123
2016 Rab25 influences functional Cav1.2 channel surface expression in arterial smooth muscle cells. American journal of physiology. Cell physiology 15 27076616
2007 Block of CaV1.2 channels by Gd3+ reveals preopening transitions in the selectivity filter. The Journal of general physiology 15 17535959