Affinage

CAV3

Caveolin-3 · UniProt P56539

Round 2 corrected
Length
151 aa
Mass
17.3 kDa
Annotated
2026-04-28
130 papers in source corpus 24 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Caveolin-3 is a muscle-specific integral membrane scaffolding protein that oligomerizes to form the structural coat of caveolae at the sarcolemma, with caveolae density directly proportional to caveolin-3 protein levels (PMID:11115849). Through its scaffolding domain, caveolin-3 directly binds and inhibits heterotrimeric G-protein α subunits (suppressing GDP/GTP exchange) (PMID:7797570), neuronal nitric oxide synthase (PMID:9353265), and receptor tyrosine kinases such as EGF-R, while conversely activating insulin receptor kinase activity (PMID:9756945); it also interacts with β-dystroglycan via a WW-like domain to link caveolae to the dystrophin-glycoprotein complex (PMID:10988290), and scaffolds dysferlin and MG53 into a tripartite membrane-repair complex (PMID:19380584). Caveolin-3 regulates cardiac ion channel function by physically associating with Nav1.5, Kir2.1, and Cav3.2 T-type calcium channels to control their surface expression, gating, and compartmentalized PKA signaling (PMID:17060380, PMID:23640888, PMID:21084288). Loss-of-function or dominant-negative CAV3 mutations cause limb-girdle muscular dystrophy type 1C, rippling muscle disease, hyperCKemia, hypertrophic cardiomyopathy, and long-QT syndrome type 9 (the latter via gain-of-function late sodium current through Nav1.5) (PMID:9537420, PMID:11431690, PMID:17060380).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1995 High

    The discovery that caveolin scaffolding domains bind inactive GDP-bound Gα subunits and suppress basal GTPase activity established the foundational concept of caveolins as direct signal-regulating scaffolds rather than passive membrane organizers.

    Evidence GST pulldown, in vitro GTPase assay, and mutational analysis of Gα activation state

    PMID:7797570

    Open questions at the time
    • Whether G-protein regulation by caveolin-3 specifically (vs caveolin-1) differs in vivo in muscle
    • Structural basis of caveolin–Gα interaction unresolved
  2. 1996 High

    Identification of caveolin-3 as a muscle-specific caveolin family member that forms high-molecular-mass oligomers and suppresses G-protein activity defined the tissue-restricted expression pattern and established CAV3 as the principal caveolar coat protein in striated muscle.

    Evidence Molecular cloning, Northern blot, velocity gradient sedimentation, and in vitro GTPase assay with caveolin-3 polypeptide

    PMID:8567687

    Open questions at the time
    • Whether caveolin-3 has unique regulatory targets not shared with caveolin-1
    • Oligomerization stoichiometry not defined
  3. 1997 High

    Demonstration that caveolin-3 scaffolding domain directly inhibits EGF receptor and PKC kinase activity, and that caveolin-3 also binds and inhibits nNOS through two distinct inhibitory sites, generalized caveolin-3's role as a multi-target enzyme inhibitor in muscle.

    Evidence In vitro kinase assays with synthetic scaffolding-domain peptides; co-IP from skeletal muscle and reconstituted NOS inhibition assays

    PMID:9353265 PMID:9374534

    Open questions at the time
    • In vivo relevance of kinase inhibition in muscle not demonstrated
    • Relative stoichiometry of caveolin-3/nNOS complexes unknown
  4. 1998 High

    Identification of CAV3 mutations as the cause of LGMD1C and the finding that caveolin-3 scaffolding domain peptides activate insulin receptor kinase revealed both the disease relevance of caveolin-3 loss and an unexpected isoform-specific kinase-activating function.

    Evidence Genetic linkage and mutation identification in LGMD1C families with immunohistochemistry; in vitro insulin receptor kinase assay with caveolin-3 peptides in 293T cells

    PMID:9537420 PMID:9756945

    Open questions at the time
    • Mechanism determining whether caveolin-3 inhibits or activates a given kinase not resolved
    • Genotype–phenotype correlation for specific CAV3 mutations incomplete
  5. 2000 High

    Caveolin-3 knockout mice showed that caveolae density is directly proportional to caveolin-3 levels and that caveolin-3 links to the dystrophin-glycoprotein complex by directly binding β-dystroglycan via a WW-like domain, integrating caveolae biogenesis with mechanical integrity of the sarcolemma.

    Evidence Gene-targeted knockout mice with electron microscopy quantification; co-IP and competitive binding assays with β-dystroglycan cytoplasmic tail

    PMID:10988290 PMID:11115849

    Open questions at the time
    • Whether caveolin-3–β-dystroglycan and dystrophin–β-dystroglycan interactions are mutually exclusive in vivo
    • Contribution of caveolin-3 to mechanical signaling vs structural integrity not separated
  6. 2001 High

    Finding that CAV3 mutations cause rippling muscle disease and that caveolin-3 scaffolds dysferlin at the sarcolemma established allelic heterogeneity at the CAV3 locus and expanded caveolin-3's function to include membrane repair protein organization.

    Evidence Genome-wide linkage in five RMD families with CAV3 mutation identification; co-IP of dysferlin–caveolin-3 from human muscle with mislocalization in LGMD1C biopsies

    PMID:11431690 PMID:11532985

    Open questions at the time
    • Direct binding interface between caveolin-3 and dysferlin not mapped
    • Mechanism linking caveolin-3 loss to mechanical hyperexcitability in RMD unknown
  7. 2006 High

    Electrophysiological reconstitution showed that LQT9-associated CAV3 mutations produce a gain-of-function increase in late sodium current through Nav1.5, establishing a cardiac channelopathy mechanism distinct from skeletal muscle disease and linking caveolin-3 to cardiac repolarization.

    Evidence Whole-cell voltage clamp in HEK293 cells stably expressing hNav1.5 co-expressed with multiple CAV3 mutants

    PMID:17060380 PMID:17275750

    Open questions at the time
    • Whether wild-type caveolin-3 directly binds Nav1.5 or acts indirectly not resolved in these studies
    • In vivo cardiac electrophysiology in CAV3 mutant animal models not performed
  8. 2008 High

    Cardiac-specific caveolin-3 overexpression mimicked ischemic preconditioning via PI3K/Akt/GSK-3β activation, while caveolin-3 knockout abolished preconditioning, demonstrating that caveolin-3 organizes pro-survival signaling platforms in the heart.

    Evidence Transgenic overexpression and knockout mice subjected to ischemia/reperfusion, with pharmacological PI3K inhibition

    PMID:18936328

    Open questions at the time
    • Whether caveolin-3 directly scaffolds PI3K or acts through intermediate adaptors not defined
    • Applicability to human cardiac ischemia not established
  9. 2009 High

    Discovery that PTRF/cavin is required for caveolin-3 stabilization and caveolae formation, and that caveolin-3 forms a tripartite membrane-repair complex with dysferlin and MG53, clarified both the upstream determinants of caveolae biogenesis and the downstream effector mechanism for sarcolemmal repair.

    Evidence PTRF patient mutations with secondary caveolin-3 loss and caveolae disruption; co-IP establishing Cav3–dysferlin–MG53 ternary complex with live-cell membrane repair assay

    PMID:19380584 PMID:19726876

    Open questions at the time
    • Stoichiometry and assembly order of the Cav3–dysferlin–MG53 complex not determined
    • Whether other cavins contribute to muscle-specific caveolae maintenance unclear
  10. 2010 High

    Immunogold EM localization of Cav3.2 T-type calcium channels to caveolae plus electrophysiological evidence that caveolin-3 suppresses Cav3.2 current and is required for PKA-dependent modulation established caveolin-3 as a compartment-specific regulator of calcium channel signaling.

    Evidence Immunogold EM, co-IP, GST pulldown, patch clamp in HEK293 and neonatal ventricular myocytes, siRNA knockdown

    PMID:21084288

    Open questions at the time
    • Structural basis of selectivity for Cav3.2 over Cav3.1 not defined
    • In vivo cardiac consequences of Cav3.2 dysregulation via caveolin-3 loss not tested
  11. 2013 High

    FRET-based proximity measurements and functional electrophysiology demonstrated that caveolin-3 physically associates with Kir2.1 and that LQT9 mutations reduce Kir2.1 surface expression, adding a potassium channel trafficking defect as a second arrhythmogenic mechanism of CAV3 mutations.

    Evidence Co-IP from human ventricular myocytes, FRET (5.6 nm distance), patch clamp, and on-cell Western for surface Kir2.1

    PMID:23640888

    Open questions at the time
    • Whether Nav1.5 and Kir2.1 regulatory defects are additive or synergistic in patient cardiomyocytes not determined
    • Direct binding domain on Kir2.1 not mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • High-resolution structural data for caveolin-3 oligomers and their complexes with ion channels and repair machinery are lacking, and whether distinct CAV3 mutations differentially affect skeletal-muscle versus cardiac caveolae remains mechanistically unresolved.
  • No atomic-resolution structure of caveolin-3 oligomer or any caveolin-3–partner complex
  • Tissue-specific modifier mechanisms explaining phenotypic variability across caveolinopathies uncharacterized
  • Relative contributions of caveolin-3 to channel trafficking vs gating modulation in native cardiomyocytes not quantitatively separated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 7 GO:0098772 molecular function regulator activity 7 GO:0005198 structural molecule activity 2
Localization
GO:0005886 plasma membrane 7 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1643685 Disease 4 R-HSA-382551 Transport of small molecules 4 R-HSA-397014 Muscle contraction 3
Partners
CACNA1HDAG1DYSFKCNJ2NOS1PTRFSCN5ATRIM72
Complex memberships
Caveolin-3–dysferlin–MG53 membrane repair complexDystrophin-glycoprotein complex

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 Caveolin-3 (CAV3) was identified as a muscle-specific member of the caveolin gene family, predominantly expressed in skeletal muscle, diaphragm, and heart. It migrates as a high molecular mass complex, co-localizes with caveolin-1, and a caveolin-3-derived polypeptide functionally suppresses basal GTPase activity of purified heterotrimeric G-proteins, indicating a direct regulatory role in G-protein signaling. Molecular cloning, Northern blot, immunofluorescence microscopy, cell fractionation, velocity gradient sedimentation, in vitro GTPase assay with caveolin-3-derived polypeptide The Journal of biological chemistry High 8567687
1995 Caveolin (caveolin-1/caveolin-3 scaffolding domain) directly interacts with the inactive GDP-bound form of heterotrimeric G-protein alpha subunits (Gs, Go, Gi) via a 41-amino acid N-terminal cytoplasmic domain (residues 61-101). This interaction suppresses basal GTPase activity by inhibiting GDP/GTP exchange, and mutational or pharmacological activation of G-alpha prevents the interaction. Cell fractionation, GST fusion protein pulldown, in vitro binding assay, GTPase activity assay, mutational analysis The Journal of biological chemistry High 7797570
1997 The scaffolding domains of caveolin-1 and caveolin-3 (but not caveolin-2) directly interact with the kinase domain of the EGF receptor via a conserved caveolin-binding motif (region IX), and inhibit EGF-R autophosphorylation and kinase activity in vitro. Similarly, caveolin scaffolding domains inhibit protein kinase C (serine/threonine kinase), suggesting caveolin-3 functions as a general kinase inhibitor within caveolae. In vitro kinase assay, direct binding with synthetic peptides, autophosphorylation assay, caveolin-binding motif analysis The Journal of biological chemistry High 9374534
1997 Neuronal nitric oxide synthase (nNOS) directly interacts with caveolin-3 in skeletal muscle, as demonstrated by co-immunoprecipitation from rat skeletal muscle homogenates. Synthetic peptides corresponding to two distinct caveolin-3 scaffolding/inhibitory domains (residues 65-84 and 109-130) potently inhibit purified recombinant nNOS catalytic activity. In vitro binding to GST-caveolin fusion protein is abolished by these peptides, indicating two distinct inhibitory interaction sites on caveolin-3. Co-immunoprecipitation from skeletal muscle, synthetic peptide inhibition assay, GST pulldown, in vitro NOS activity assay The Journal of biological chemistry High 9353265
1998 Mutations in the CAV3 gene cause autosomal dominant limb-girdle muscular dystrophy type 1C (LGMD1C): a missense mutation in the membrane-spanning region and a micro-deletion in the scaffolding domain were identified. These mutations are associated with severe deficiency of caveolin-3 in muscle fibers, suggesting they interfere with caveolin-3 oligomerization and disrupt caveolae formation at the sarcolemma. Genetic linkage, mutation identification (missense + microdeletion), immunohistochemistry, Western blot, electron microscopy of muscle biopsies Nature genetics High 9537420
1998 Caveolin-3 co-purifies with dystrophin and a fraction of caveolin-3 is a dystrophin-associated protein in skeletal muscle. Mutations in caveolin-3 (G55S and C71W) map to a functionally important domain. Caveolin-3 deficiency is associated with muscular dystrophy. Co-purification with dystrophin complex, mutation screening (PCR/sequencing), immunohistochemistry Human molecular genetics Medium 9536092
1998 Caveolin-3 overexpression augments insulin-stimulated phosphorylation of insulin receptor substrate-1 (IRS-1) in 293T cells. Peptides from the caveolin-3 scaffolding domain stimulate insulin receptor kinase activity toward IRS-1 approximately 17-fold in vitro, and the insulin receptor directly binds immobilized caveolin-3 peptides. This defines caveolin-3 as an activator (not inhibitor) of insulin receptor signaling, in contrast to its inhibitory role on other kinases. Overexpression in 293T cells, in vitro kinase activity assay with scaffolding domain peptides, direct binding assay with immobilized peptides The Journal of biological chemistry High 9756945
2000 Caveolin-3 directly interacts with β-dystroglycan, an integral membrane component of the dystrophin-glycoprotein complex, via a novel WW-like domain within caveolin-3 that recognizes the PPXY motif at the C-terminus of β-dystroglycan. Caveolin-3 co-localizes, co-fractionates, and co-immunoprecipitates with β-dystroglycan, and can competitively block dystrophin binding to β-dystroglycan. Co-immunoprecipitation, co-fractionation, direct binding assay with β-dystroglycan cytoplasmic tail fusion protein, competitive inhibition assay The Journal of biological chemistry High 10988290
2000 Caveolin-3 deficiency in mice causes muscle degeneration (soleus and diaphragm), demonstrating that caveolin-3 is required for skeletal muscle integrity. Caveolae density in skeletal muscle plasma membrane is proportional to caveolin-3 protein levels, establishing a direct structural role for caveolin-3 in caveolae biogenesis in muscle. Gene targeting/knockout mice, electron microscopy of sarcolemmal caveolae, histological analysis of muscle degeneration, Western blot Human molecular genetics High 11115849
2000 A dominant-negative caveolin-3 mutation (A46T in the caveolin signature sequence) prevents membrane localization of caveolin-3 and causes secondary decrease in neuronal nitric oxide synthase and α-dystroglycan expression in muscle, linking caveolin-3's scaffolding function to maintenance of the dystrophin-glycoprotein complex integrity. Mutation identification, immunohistochemistry, Western blot for nNOS and α-dystroglycan in patient muscle biopsy, dominant-negative analysis Human molecular genetics Medium 11001938
2000 A CAV3 gene mutation causes partial caveolin-3 deficiency (hyperCKemia) without muscle weakness, establishing that partial loss-of-function of caveolin-3 results in a distinct clinical phenotype with reduced sarcolemmal caveolin-3 expression. Mutation identification, immunohistochemistry, quantitative immunoblot in muscle biopsies Neurology Medium 10746614
2001 Dysferlin co-immunoprecipitates with caveolin-3 from biopsied normal human skeletal muscle, establishing a physical interaction between these two sarcolemmal proteins. Mutations in CAV3 cause abnormal dysferlin localization in LGMD1C muscles, suggesting caveolin-3 scaffolds dysferlin for proper membrane targeting. The dysferlin sequence contains seven putative caveolin-3 scaffold-binding motifs. Co-immunoprecipitation from human muscle biopsies, immunostaining of patient muscle, sequence analysis Human molecular genetics Medium 11532985
2001 Missense mutations in CAV3 cause hereditary rippling muscle disease (RMD), a mechanically-triggered skeletal muscle contraction disorder, establishing allelic heterogeneity between RMD and LGMD1C at the CAV3 locus. Genome-wide linkage analysis, positional candidate gene sequencing, identification of missense mutations in CAV3 in five RMD families Nature genetics High 11431690
2003 A 3-bp microdeletion in CAV3 (Phe97del in the transmembrane domain) causes severe caveolin-3 deficiency and caveolar disorganization in skeletal muscle, but only ~40% reduction in myocardial caveolin-3 with preserved cardiac caveolar structures, demonstrating tissue-specific differences in caveolin-3 expression and function between skeletal and cardiac muscle. Genetic analysis, immunohistochemistry, Western blot, electron microscopy of skeletal muscle and heart biopsies Neurology Medium 14663034
2004 A caveolin-3 mutation (Thr63Ser) associated with familial hypertrophic cardiomyopathy reduces cell surface expression of caveolin-3 (GFP-tagged construct), establishing a loss-of-membrane-targeting mechanism in HCM caused by CAV3 mutations. Mutation identification by genetic screening, GFP-tagged CAV3 expression and cellular localization analysis Biochemical and biophysical research communications Medium 14672715
2006 Four novel CAV3 mutations cause long-QT syndrome type 9 (LQT9) by producing a 2- to 3-fold gain-of-function increase in late sodium current (I_Na,L) through the cardiac sodium channel hNav1.5, co-expressed in HEK293 cells. This establishes mutant caveolin-3 as a functional regulator of cardiac sodium channel gating, acting to increase persistent late Na+ current and prolong cardiac repolarization. Mutation screening (DHPLC + sequencing) in 905 LQTS patients, site-directed mutagenesis, heterologous expression in HEK293 cells stably expressing hNav1.5, whole-cell voltage-clamp electrophysiology Circulation High 17060380
2006 Three CAV3 mutations (V14L, T78M, L79R) found in SIDS cases cause a ~5-fold increase in late sodium current through hNav1.5 in a heterologous expression system, providing an LQT3-like arrhythmogenic mechanism for sudden infant death. Post-mortem genetic testing of SIDS cases, site-directed mutagenesis, voltage-clamp electrophysiology in HEK293 cells co-expressing hNav1.5 and mutant CAV3 Heart rhythm High 17275750
2008 Cardiac-specific overexpression of caveolin-3 is sufficient to induce endogenous cardiac protection against ischemia/reperfusion injury, mimicking ischemic preconditioning. This protection is associated with increased caveolae formation and elevated basal phosphorylation of Akt and GSK-3β, and is blocked by the PI3-kinase inhibitor wortmannin. Caveolin-3 knockout mice lack both endogenous protection and ischemic preconditioning-induced protection. Transgenic mice with cardiac-specific Cav-3 overexpression, Cav-3 knockout mice, ischemia/reperfusion infarct model, adenovirus-mediated Cav-3 expression, Western blot for survival kinases, pharmacological inhibition Circulation High 18936328
2009 PTRF (cavin) mutations in humans cause secondary deficiency and mislocalization of all three caveolin family members (including caveolin-3) in skeletal muscle, with loss of caveolae structures and resultant muscular dystrophy with generalized lipodystrophy. Expression constructs recapitulating human mutations showed PTRF mislocalization and disrupted physical interaction with caveolins, establishing PTRF as essential for caveolae formation and caveolin-3 stabilization. Patient genetic analysis, immunohistochemistry, electron microscopy of muscle biopsies, overexpression of mutant PTRF constructs in myoblasts, co-immunoprecipitation The Journal of clinical investigation High 19726876
2009 Caveolin-3 directly interacts with dysferlin and MG53 (TRIM72) to form a tripartite complex essential for skeletal muscle membrane repair. Mutations in caveolin-3 (P104L, R26Q) that cause Golgi retention result in aberrant localization of both MG53 and dysferlin in a dominant-negative fashion, impairing membrane repair patch formation at sites of cell injury. Co-immunoprecipitation, dominant-negative expression of CAV3 mutants, live-cell imaging of vesicle trafficking to injury sites, membrane repair assay in skeletal muscle cells The Journal of biological chemistry High 19380584
2010 Caveolin-3 co-localizes with Cav3.2 T-type calcium channels at caveolae in ventricular myocytes (demonstrated by immunogold EM), and co-immunoprecipitates with both Cav3.1 and Cav3.2 channels from neonatal ventricular myocytes and HEK293 cells. GST pulldown confirmed the N-terminus of caveolin-3 interacts with Cav3.2. Co-expression of caveolin-3 significantly decreases peak Cav3.2 current density (but not Cav3.1), and PKA-dependent stimulation of T-type Ca2+ current is abolished by siRNA knockdown of caveolin-3, establishing caveolin-3 as a compartment-specific regulator of Cav3.2 channel activity and PKA-mediated signaling. Immunogold electron microscopy, co-immunoprecipitation, GST pulldown, whole-cell patch clamp in HEK293 and neonatal ventricular myocytes, siRNA knockdown, adenovirus overexpression The Journal of biological chemistry High 21084288
2013 Caveolin-3 physically associates with the inward-rectifier potassium channel Kir2.1 in human ventricular myocytes and heterologous systems, demonstrated by co-immunoprecipitation and FRET analysis (molecular distance 5.6 ± 0.4 nm). LQT9-associated CAV3 mutations (F97C, T78M, P104L) decrease Kir2.1 current density by 30-60% through reduced Kir2.1 cell surface expression, providing an additional arrhythmogenic mechanism beyond the previously described late sodium current increase. Co-immunoprecipitation from human ventricular myocytes, confocal colocalization, FRET analysis, whole-cell voltage clamp, on-cell Western blot for surface expression The Journal of biological chemistry High 23640888
2004 Junctophilin type 2 (JP-2) localizes to caveolin-rich membranes and associates with caveolin-3 in cardiac muscle, as demonstrated by co-fractionation. JP-2 expression is upregulated during normal cardiac development and downregulated in hypertrophic and dilated cardiomyopathy models, linking caveolin-3-associated membrane domains to junctional membrane complex formation and Ca2+-induced Ca2+ release. Subcellular fractionation into caveolin-rich membranes, co-fractionation analysis, Western blot during cardiac development and in cardiomyopathy models Biochemical and biophysical research communications Medium 15541368
2016 CAV3 mutations (p.T78M, p.V14I, p.F41S, p.F54V) identified by next-generation sequencing cause exercise intolerance, myalgia, and rhabdomyolysis with >50% reduction of caveolin-3 protein on immunoblot, expanding the caveolinopathy phenotypic spectrum. Immunoblotting was more sensitive than immunohistochemistry for detecting caveolin-3 reduction. Next-generation sequencing, immunoblotting, immunohistochemistry of skeletal muscle biopsies, clinical phenotyping Neuromuscular disorders Medium 27312022

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
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
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2020 A reference map of the human binary protein interactome. Nature 849 32296183
1995 VIP21/caveolin is a cholesterol-binding protein. Proceedings of the National Academy of Sciences of the United States of America 786 7479780
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1996 Molecular cloning of caveolin-3, a novel member of the caveolin gene family expressed predominantly in muscle. The Journal of biological chemistry 601 8567687
1995 Evidence for a regulated interaction between heterotrimeric G proteins and caveolin. The Journal of biological chemistry 570 7797570
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
1995 De novo formation of caveolae in lymphocytes by expression of VIP21-caveolin. Proceedings of the National Academy of Sciences of the United States of America 513 7567992
1992 VIP21, a 21-kD membrane protein is an integral component of trans-Golgi-network-derived transport vesicles. The Journal of cell biology 481 1512286
1998 Mutations in the caveolin-3 gene cause autosomal dominant limb-girdle muscular dystrophy. Nature genetics 462 9537420
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
1995 VIP21-caveolin, a membrane protein constituent of the caveolar coat, oligomerizes in vivo and in vitro. Molecular biology of the cell 405 7579702
2006 Mutant caveolin-3 induces persistent late sodium current and is associated with long-QT syndrome. Circulation 367 17060380
2004 Silencing of the Cav3.2 T-type calcium channel gene in sensory neurons demonstrates its major role in nociception. The EMBO journal 366 15616581
2007 Prevalence of long-QT syndrome gene variants in sudden infant death syndrome. Circulation 363 17210839
2009 Human PTRF mutations cause secondary deficiency of caveolins resulting in muscular dystrophy with generalized lipodystrophy. The Journal of clinical investigation 302 19726876
1998 Caveolin is an activator of insulin receptor signaling. The Journal of biological chemistry 258 9756945
2009 Membrane repair defects in muscular dystrophy are linked to altered interaction between MG53, caveolin-3, and dysferlin. The Journal of biological chemistry 238 19380584
2006 Bradycardia and slowing of the atrioventricular conduction in mice lacking CaV3.1/alpha1G T-type calcium channels. Circulation research 231 16690884
2014 The deubiquitinating enzyme USP5 modulates neuropathic and inflammatory pain by enhancing Cav3.2 channel activity. Neuron 214 25189210
1997 Interaction of neuronal nitric-oxide synthase with caveolin-3 in skeletal muscle. Identification of a novel caveolin scaffolding/inhibitory domain. The Journal of biological chemistry 213 9353265
2011 Toward an understanding of the protein interaction network of the human liver. Molecular systems biology 207 21988832
2001 The sarcolemmal proteins dysferlin and caveolin-3 interact in skeletal muscle. Human molecular genetics 194 11532985
1992 The sequence of human caveolin reveals identity with VIP21, a component of transport vesicles. FEBS letters 182 1360410
2000 Caveolin-3 directly interacts with the C-terminal tail of beta -dystroglycan. Identification of a central WW-like domain within caveolin family members. The Journal of biological chemistry 175 10988290
1998 Caveolin-3 in muscular dystrophy. Human molecular genetics 173 9536092
2008 Transcriptional upregulation of Cav3.2 mediates epileptogenesis in the pilocarpine model of epilepsy. The Journal of neuroscience : the official journal of the Society for Neuroscience 171 19052226
2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip. American journal of human genetics 164 19913121
2017 Dorsal root ganglion neurons become hyperexcitable and increase expression of voltage-gated T-type calcium channels (Cav3.2) in paclitaxel-induced peripheral neuropathy. Pain 163 27902567
1995 A photo-reactive derivative of ganglioside GM1 specifically cross-links VIP21-caveolin on the cell surface. FEBS letters 163 7498456
2015 The Low-Threshold Calcium Channel Cav3.2 Determines Low-Threshold Mechanoreceptor Function. Cell reports 162 25600872
2006 Novel mechanism for sudden infant death syndrome: persistent late sodium current secondary to mutations in caveolin-3. Heart rhythm 161 17275750
1996 Oligomerization of VIP21-caveolin in vitro is stabilized by long chain fatty acylation or cholesterol. FEBS letters 159 8690074
2009 Caveolinopathies: from the biology of caveolin-3 to human diseases. European journal of human genetics : EJHG 158 19584897
1994 VIP21/caveolin, glycosphingolipid clusters and the sorting of glycosylphosphatidylinositol-anchored proteins in epithelial cells. The EMBO journal 152 8306971
2001 Mutations in CAV3 cause mechanical hyperirritability of skeletal muscle in rippling muscle disease. Nature genetics 145 11431690
2004 Caveolinopathies: mutations in caveolin-3 cause four distinct autosomal dominant muscle diseases. Neurology 141 14981167
2011 Presynaptic HCN1 channels regulate Cav3.2 activity and neurotransmission at select cortical synapses. Nature neuroscience 139 21358644
2000 Caveolin-3 deficiency causes muscle degeneration in mice. Human molecular genetics 138 11115849
2008 Cardiac-specific overexpression of caveolin-3 induces endogenous cardiac protection by mimicking ischemic preconditioning. Circulation 123 18936328
2004 Junctophilin type 2 is associated with caveolin-3 and is down-regulated in the hypertrophic and dilated cardiomyopathies. Biochemical and biophysical research communications 119 15541368
2004 Identification and functional analysis of a caveolin-3 mutation associated with familial hypertrophic cardiomyopathy. Biochemical and biophysical research communications 111 14672715
2000 Mutation in the CAV3 gene causes partial caveolin-3 deficiency and hyperCKemia. Neurology 110 10746614
2000 Dissociation of the dystroglycan complex in caveolin-3-deficient limb girdle muscular dystrophy. Human molecular genetics 110 11001938
2013 Surface expression and function of Cav3.2 T-type calcium channels are controlled by asparagine-linked glycosylation. Pflugers Archiv : European journal of physiology 91 23503728
2009 Functional coupling between mGluR1 and Cav3.1 T-type calcium channels contributes to parallel fiber-induced fast calcium signaling within Purkinje cell dendritic spines. The Journal of neuroscience : the official journal of the Society for Neuroscience 86 19657020
2015 A Recurrent Mutation in CACNA1G Alters Cav3.1 T-Type Calcium-Channel Conduction and Causes Autosomal-Dominant Cerebellar Ataxia. American journal of human genetics 85 26456284
2011 Nerve terminal nicotinic acetylcholine receptors initiate quantal GABA release from perisomatic interneurons by activating axonal T-type (Cav3) Ca²⁺ channels and Ca²⁺ release from stores. The Journal of neuroscience : the official journal of the Society for Neuroscience 80 21940446
2006 CaV3.2 is the major molecular substrate for redox regulation of T-type Ca2+ channels in the rat and mouse thalamus. The Journal of physiology 77 16644797
1994 VIP21-Caveolin, a protein of the trans-Golgi network and caveolae. FEBS letters 77 8206165
2013 Chronic hypoxia selectively enhances L- and T-type voltage-dependent Ca2+ channel activity in pulmonary artery by upregulating Cav1.2 and Cav3.2. American journal of physiology. Lung cellular and molecular physiology 73 23686856
2012 Hydrogen sulfide-induced mechanical hyperalgesia and allodynia require activation of both Cav3.2 and TRPA1 channels in mice. British journal of pharmacology 70 22300342
2011 Association of the α(2)δ(1) subunit with Ca(v)3.2 enhances membrane expression and regulates mechanically induced ATP release in MLO-Y4 osteocytes. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 69 21638318
2021 Targeting T-type/CaV3.2 channels for chronic pain. Translational research : the journal of laboratory and clinical medicine 68 33422652
2012 T-type voltage-activated calcium channel Cav3.1, but not Cav3.2, is involved in the inhibition of proliferation and apoptosis in MCF-7 human breast cancer cells. International journal of oncology 68 22469755
2007 Temperature-dependent modulation of CaV3 T-type calcium channels by protein kinases C and A in mammalian cells. The Journal of biological chemistry 68 17855364
2005 Expression of voltage sensitive calcium channel (VSCC) L-type Cav1.2 (alpha1C) and T-type Cav3.2 (alpha1H) subunits during mouse bone development. Developmental dynamics : an official publication of the American Association of Anatomists 67 16059921
2012 Transcriptional regulation of T-type calcium channel CaV3.2: bi-directionality by early growth response 1 (Egr1) and repressor element 1 (RE-1) protein-silencing transcription factor (REST). The Journal of biological chemistry 62 22431737
2014 Ca(V)3.2 channels and the induction of negative feedback in cerebral arteries. Circulation research 60 25085940
2008 Activation of corticotropin-releasing factor receptor 1 selectively inhibits CaV3.2 T-type calcium channels. Molecular pharmacology 59 18292205
2014 Cav3.2 T-type calcium channel is required for the NFAT-dependent Sox9 expression in tracheal cartilage. Proceedings of the National Academy of Sciences of the United States of America 58 24778262
1999 The "early-sorting" endocytic compartment of rat hepatocytes is involved in the intracellular pathway of caveolin-1 (VIP-21). Hepatology (Baltimore, Md.) 55 10347129
2006 Augmentation of Cav3.2 T-type calcium channel activity by cAMP-dependent protein kinase A. The Journal of pharmacology and experimental therapeutics 53 16569752
2013 Low voltage activation of KCa1.1 current by Cav3-KCa1.1 complexes. PloS one 51 23626738
2014 Endogenous and exogenous hydrogen sulfide facilitates T-type calcium channel currents in Cav3.2-expressing HEK293 cells. Biochemical and biophysical research communications 49 24508802
2015 Phosphorylation of the Cav3.2 T-type calcium channel directly regulates its gating properties. Proceedings of the National Academy of Sciences of the United States of America 47 26483470
2013 Age-related downregulation of the CaV3.1 T-type calcium channel as a mediator of amyloid beta production. Neurobiology of aging 46 24268883
2015 Expression and Regulation of Cav3.2 T-Type Calcium Channels during Inflammatory Hyperalgesia in Mouse Dorsal Root Ganglion Neurons. PloS one 45 25974104
2013 The interaction of caveolin 3 protein with the potassium inward rectifier channel Kir2.1: physiology and pathology related to long qt syndrome 9 (LQT9). The Journal of biological chemistry 44 23640888
2017 Identification of interleukin-1 beta as a key mediator in the upregulation of Cav3.2-USP5 interactions in the pain pathway. Molecular pain 43 28741432
2004 Functional impact of alternative splicing of human T-type Cav3.3 calcium channels. Journal of neurophysiology 42 15254077
2016 Suppression of Sleep Spindle Rhythmogenesis in Mice with Deletion of CaV3.2 and CaV3.3 T-type Ca(2+) Channels. Sleep 41 26612388
2015 CaV3.2 calcium channels control NMDA receptor-mediated transmission: a new mechanism for absence epilepsy. Genes & development 41 26220996
2009 Five different profiles of dihydropyridines in blocking T-type Ca(2+) channel subtypes (Ca(v)3.1 (alpha(1G)), Ca(v)3.2 (alpha(1H)), and Ca(v)3.3 (alpha(1I))) expressed in Xenopus oocytes. European journal of pharmacology 41 19401195
2007 Selective inhibition of Cav3.3 T-type calcium channels by Galphaq/11-coupled muscarinic acetylcholine receptors. The Journal of biological chemistry 41 17535809
2015 CaV1.2/CaV3.x channels mediate divergent vasomotor responses in human cerebral arteries. The Journal of general physiology 39 25918359
2015 Genetic ablation of CaV3.2 channels enhances the arterial myogenic response by modulating the RyR-BKCa axis. Arteriosclerosis, thrombosis, and vascular biology 39 26069238
2013 The Cav3-Kv4 complex acts as a calcium sensor to maintain inhibitory charge transfer during extracellular calcium fluctuations. The Journal of neuroscience : the official journal of the Society for Neuroscience 39 23637173
2014 Hydrogen sulfide inhibits Cav3.2 T-type Ca2+ channels. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 38 25183670
2010 Caveolin-3 regulates protein kinase A modulation of the Ca(V)3.2 (alpha1H) T-type Ca2+ channels. The Journal of biological chemistry 38 21084288
2022 Histone methylation-mediated microRNA-32-5p down-regulation in sensory neurons regulates pain behaviors via targeting Cav3.2 channels. Proceedings of the National Academy of Sciences of the United States of America 36 35353623
2013 Functional coupling between large-conductance potassium channels and Cav3.2 voltage-dependent calcium channels participates in prostate cancer cell growth. Biology open 36 24143281
2009 Protein kinase A activity controls the regulation of T-type CaV3.2 channels by Gbetagamma dimers. The Journal of biological chemistry 36 19131331
2019 Tumour-specific amplitude-modulated radiofrequency electromagnetic fields induce differentiation of hepatocellular carcinoma via targeting Cav3.2 T-type voltage-gated calcium channels and Ca2+ influx. EBioMedicine 35 31160272
2009 Structural determinants of the high affinity extracellular zinc binding site on Cav3.2 T-type calcium channels. The Journal of biological chemistry 35 19940152
2016 Low-Voltage-Activated CaV3.1 Calcium Channels Shape T Helper Cell Cytokine Profiles. Immunity 34 27037192
2019 Nerve injury elevates functional Cav3.2 channels in superficial spinal dorsal horn. Molecular pain 33 30803310
2018 CACHD1 is an α2δ-Like Protein That Modulates CaV3 Voltage-Gated Calcium Channel Activity. The Journal of neuroscience : the official journal of the Society for Neuroscience 33 30181139
2016 The voltage gated Ca(2+)-channel Cav3.2 and therapeutic responses in breast cancer. Cancer cell international 33 27034617
2016 CAV3 mutations causing exercise intolerance, myalgia and rhabdomyolysis: Expanding the phenotypic spectrum of caveolinopathies. Neuromuscular disorders : NMD 33 27312022
2015 Hydrogen sulfide-induced itch requires activation of Cav3.2 T-type calcium channel in mice. Scientific reports 33 26602811
2013 Carbon monoxide inhibition of Cav3.2 T-type Ca2+ channels reveals tonic modulation by thioredoxin. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 33 23671274
2022 Cav3.1-driven bursting firing in ventromedial hypothalamic neurons exerts dual control of anxiety-like behavior and energy expenditure. Molecular psychiatry 32 35318460
2005 Subtype switching of T-type Ca 2+ channels from Cav3.2 to Cav3.1 during differentiation of embryonic stem cells to cardiac cell lineage. Circulation journal : official journal of the Japanese Circulation Society 32 16195632
2014 Epigallocatechin-3-gallate elicits Ca2+ spike in MCF-7 breast cancer cells: essential role of Cav3.2 channels. Cell calcium 31 25260713
2010 Free radical signalling underlies inhibition of CaV3.2 T-type calcium channels by nitrous oxide in the pain pathway. The Journal of physiology 31 21059758
2016 Modulation of Cav3.2 T-type calcium channel permeability by asparagine-linked glycosylation. Channels (Austin, Tex.) 30 26745591
2015 Functional upregulation of the H2S/Cav3.2 channel pathway accelerates secretory function in neuroendocrine-differentiated human prostate cancer cells. Biochemical pharmacology 30 26256074
2014 Roles of Cav3.2 and TRPA1 channels targeted by hydrogen sulfide in pancreatic nociceptive processing in mice with or without acute pancreatitis. Journal of neuroscience research 30 25267397
2003 A CAV3 microdeletion differentially affects skeletal muscle and myocardium. Neurology 30 14663034
2017 Calmodulin regulates Cav3 T-type channels at their gating brake. The Journal of biological chemistry 29 28972185
2022 Voltage-dependent CaV3.2 and CaV2.2 channels in nociceptive pathways. Pflugers Archiv : European journal of physiology 28 35043234
2008 Alternative splicing within the I-II loop controls surface expression of T-type Ca(v)3.1 calcium channels. FEBS letters 27 18930057
2018 The Low-Threshold Calcium Channel Cav3.2 Mediates Burst Firing of Mature Dentate Granule Cells. Cerebral cortex (New York, N.Y. : 1991) 26 29790938
2019 SUMOylation regulates USP5-Cav3.2 calcium channel interactions. Molecular brain 25 31455361
2014 The expression pattern of a Cav3-Kv4 complex differentially regulates spike output in cerebellar granule cells. The Journal of neuroscience : the official journal of the Society for Neuroscience 24 24966380
2012 β-Adrenergic stimulation increases Cav3.1 activity in cardiac myocytes through protein kinase A. PloS one 24 22808078
2010 Regulation and function of Cav3.1 T-type calcium channels in IGF-I-stimulated pulmonary artery smooth muscle cells. American journal of physiology. Cell physiology 24 21148410
2008 17 beta-estradiol modulates expression of low-voltage-activated Ca(V)3.2 T-type calcium channel via extracellularly regulated kinase pathway in cardiomyocytes. Endocrinology 24 18832095
2018 Melatonin-mediated inhibition of Cav3.2 T-type Ca2+ channels induces sensory neuronal hypoexcitability through the novel protein kinase C-eta isoform. Journal of pineal research 23 29437250
2018 Caveolae Link CaV3.2 Channels to BKCa-Mediated Feedback in Vascular Smooth Muscle. Arteriosclerosis, thrombosis, and vascular biology 23 30354206
2010 Involvement of CaV3.1 T-type calcium channels in cell proliferation in mouse preadipocytes. American journal of physiology. Cell physiology 23 20457833
2010 Characterization of the gating brake in the I-II loop of CaV3 T-type calcium channels. Channels (Austin, Tex.) 23 21099341
2017 Zinc deficiency promotes cystitis-related bladder pain by enhancing function and expression of Cav3.2 in mice. Toxicology 22 29129814
2014 Cav3 T-type channels: regulators for gating, membrane expression, and cation selectivity. Pflugers Archiv : European journal of physiology 22 24515291
2006 Determinants of the differential gating properties of Cav3.1 and Cav3.3 T-type channels: a role of domain IV? Neuroscience 22 16996222
2022 A Synthetically Accessible Small-Molecule Inhibitor of USP5-Cav3.2 Calcium Channel Interactions with Analgesic Properties. ACS chemical neuroscience 21 35113527
2021 Neuromedin B receptor stimulation of Cav3.2 T-type Ca2+ channels in primary sensory neurons mediates peripheral pain hypersensitivity. Theranostics 21 34646374
2020 Channelopathies of voltage-gated L-type Cav1.3/α1D and T-type Cav3.1/α1G Ca2+ channels in dysfunction of heart automaticity. Pflugers Archiv : European journal of physiology 21 32601767
2005 Contrasting effects of Cd2+ and Co2+ on the blocking/unblocking of human Cav3 channels. The Journal of membrane biology 21 16477530
2024 α-Synuclein oligomers potentiate neuroinflammatory NF-κB activity and induce Cav3.2 calcium signaling in astrocytes. Translational neurodegeneration 20 38378800
2019 T-Type Cav3.1 Channels Mediate Progression and Chemotherapeutic Resistance in Glioblastoma. Cancer research 20 30755443
2016 Colocalization of insulin-like growth factor-1 receptor and T type Cav3.2 channel in dorsal root ganglia in chronic inflammatory pain mouse model. Neuroreport 20 27213932
2013 Mitochondrial Ca2+ uptake from plasma membrane Cav3.2 protein channels contributes to ischemic toxicity in PC12 cells. The Journal of biological chemistry 20 23508951
2009 CCR2 receptor ligands inhibit Cav3.2 T-type calcium channels. Molecular pharmacology 20 19864434
2015 Regulation of neuronal cav3.1 channels by cyclin-dependent kinase 5 (Cdk5). PloS one 19 25760945
2013 Physical interaction between calcineurin and Cav3.2 T-type Ca2+ channel modulates their functions. FEBS letters 19 23669360
2004 Multiple structural elements contribute to the slow kinetics of the Cav3.3 T-type channel. The Journal of biological chemistry 19 15016809