| 1995 |
Vinculin (VCL) contains an intramolecular head-tail autoinhibitory interaction: the 95 kDa head domain masks an F-actin binding site located in the 30 kDa carboxy-terminal tail domain (residues 811–1066). Intact vinculin does not cosediment with F-actin, but isolated tail fragments do, and the head fragment inhibits this interaction, demonstrating that activation requires disruption of the head-tail association. |
Cosedimentation assays, crosslinking, transmission electron microscopy, bacterially expressed domain fragments, proteolytic fragmentation |
Nature |
High |
7816144
|
| 1999 |
Paxillin LD motifs function as selective protein-binding interfaces; LD motifs mediate direct binding to vinculin as part of focal adhesion scaffold assembly, implicating vinculin in paxillin-organized cytoskeletal remodeling at focal adhesions. |
GST pulldown, microinjection of LD motif peptides, GFP localization, cell migration wound assay |
The Journal of Cell Biology |
High |
10330411
|
| 2002 |
The Arp2/3 complex directly binds to the hinge region of vinculin in a phosphatidylinositol-4,5-bisphosphate- and Rac1-dependent manner. This interaction recruits Arp2/3 to new integrin adhesion sites and promotes lamellipodial protrusion and cell spreading; a point mutation in the hinge region selectively blocks Arp2/3 binding and reduces spreading on fibronectin. |
Co-immunoprecipitation, GST pulldown, domain mapping with point mutagenesis, vinculin-null cell rescue, spreading/protrusion assays |
The Journal of Cell Biology |
High |
12473693
|
| 1992 |
The vinculin gene (VCL) maps to chromosomal band 10q22.1–q23, distal to D10S22, established by somatic hybrid panel hybridization, genetic recombination mapping in MEN2 families, and flow-sorted translocation chromosome hybridization. |
Somatic cell hybrid panel, genetic linkage mapping, flow-sorted chromosome hybridization |
Genomics |
Medium |
1505973
|
| 2007 |
Vinculin head domain regulates integrin dynamics and clustering while the tail domain links focal adhesions to the actin force-transmission machinery. Vinculin constructs with unmasked head and tail binding sites induce dramatic focal adhesion growth through direct interaction with talin, which promotes integrin clustering and increases integrin residency time. Paxillin recruitment at focal adhesions occurs independently of the vinculin tail's paxillin-binding site. |
Vinculin head/tail mutant expression, FRAP, integrin clustering assays, co-immunoprecipitation, TIRF microscopy in vinculin-null cells |
The Journal of Cell Biology |
High |
18056416
|
| 2012 |
Vinculin associates with VE-cadherin-based adherens junctions (focal adherens junctions, FAJs) that are attached to radial F-actin bundles and subjected to actomyosin-generated pulling forces. Vinculin protects VE-cadherin junctions from opening during force-dependent remodeling induced by VEGF, TNF-α, or thrombin. FAJ formation requires Rho-Rock-actomyosin contractility but not vinculin itself; however, vinculin loss results in junction opening under force. |
Live-cell imaging, vinculin-null endothelial cells, Rho-Rock inhibition, α-catenin vinculin-binding-deficient mutant, tension measurement |
The Journal of Cell Biology |
High |
22391038
|
| 2015 |
ZO-1 depletion in endothelial cells reduces tension on VE-cadherin and causes loss of junctional mechanotransducers including vinculin, inducing vinculin dissociation from the α-catenin–VE-cadherin complex. This places vinculin downstream of ZO-1–JACOP–p114RhoGEF–Rho signaling in regulation of actomyosin-dependent junction tension. |
siRNA knockdown, FRET tension sensors, immunofluorescence, co-immunoprecipitation, endothelial barrier assays |
The Journal of Cell Biology |
High |
25753039
|
| 2017 |
Mechanistic review consolidating that vinculin is recruited to and activated at both integrin-based focal adhesions and cadherin-based adherens junctions; its autoinhibited head-tail conformation is relieved by simultaneous binding of talin (head) and actin (tail), enabling force transmission and cytoskeletal linkage at adhesion complexes. |
Review integrating structural, biochemical, and cell biological evidence |
Cellular and Molecular Life Sciences |
Medium |
28401269
|
| 2019 |
In contracting cardiomyocytes, mechanical forces from the heartbeat regulate vinculin (VCL) localization and activation. VCL is essential for myofilament maturation in the developing zebrafish heart. Interactome analysis in contracting vs. non-contracting cardiomyocytes identified slingshot protein phosphatase SSH1 as a VCL interactor; VCL recruits SSH1 and its effector cofilin (CFL) to regulate F-actin rearrangement and promote sarcomere myofilament maturation. |
Zebrafish genetic model (vcl knockout), quantitative interactomics (mass spectrometry), co-immunoprecipitation, F-actin staining, live imaging of contracting vs. non-contracting hearts |
Developmental Cell |
High |
31495694
|
| 2021 |
Loss-of-function (p.D256fs) and gain-of-function (p.L555V) VCL variants cause human neural tube defects. p.L555V increases vinculin protein stability and enhances PCP pathway regulation and cell migration, demonstrating that both reduced and excess VCL function disrupt neural tube closure. |
Targeted NGS in NTD cohort, in vitro functional assays (PCP pathway reporter, migration assays), protein stability analysis |
Molecular Genetics & Genomic Medicine |
Medium |
33491343
|
| 2021 |
Vinculin contains conserved tankyrase-binding motifs (TBMs) in vertebrates (absent in C. elegans). Tankyrase (TNKS) localizes to the plasma membrane belt in epithelial cells, a VCL pool is covalently PARylated (poly-ADP-ribosylated), and overexpression of a VCL TBM-II point mutant induces mesenchymal-like cell shape changes, suggesting TNKS-mediated PARylation of VCL regulates epithelial adherens junction integrity and cell shape. |
Sequence conservation analysis, TNKS inhibitor treatment, immunocytofluorescence, subcellular fractionation, PAR affinity precipitation + western blot, transfection of TBM mutant VCL |
PeerJ |
Medium |
34123588
|
| 2024 |
miR-6721-5p directly interacts with the 3'-UTR of meta-VCL (the muscle-specific large splice isoform of VCL) and negatively regulates its expression. Upregulation of miR-6721-5p in CAD patients correlates with reduced meta-VCL and decreased anti-inflammatory cytokines IL-10 and TNF-α. |
Dual-luciferase 3'-UTR reporter assay, qPCR, ELISA for cytokines, bioinformatics, ROC curve analysis of serum samples |
Non-coding RNA Research |
Medium |
39296643
|
| 2023 |
miR-29a-3p directly targets the 3'-UTR of VCL (and CTNNB1) in nasal epithelial cells, reducing VCL protein expression. VCL and β-catenin contribute to adherens junction and tight junction integrity of nasal mucosa; miR-29a-3p upregulation in allergic rhinitis disrupts epithelial barrier function, which is partially rescued by miR-29a-3p antagomir in OVA-induced AR mice. |
Dual-luciferase reporter assay, miRNA mimic/inhibitor transfection, OVA-induced AR mouse model, qPCR, antagomir treatment, barrier function assays |
International Immunopharmacology |
Medium |
37262956
|
| 2025 |
VCL plasma levels are elevated in Omicron SARS-CoV-2 infection and correlate with inflammatory markers and lung exudation. Anti-VCL intervention in a rat lung injury model reduces plasma VCL levels, mitigates alveolar edema, and restores alveolar-capillary barrier integrity, demonstrating that VCL modulation affects vascular leakage and extravasation. |
Multi-omics proteomics/metabolomics of human plasma, rat lung injury model, anti-VCL antibody intervention, histological staining, electron microscopy |
Nature Communications |
Medium |
40268929
|
| 2024 |
VCL is identified as a novel CRBN (cereblon) neosubstrate degradable by molecular glue degraders; ubiquitinomics analysis confirms VCL ubiquitylation upon treatment with phenyl glutarimide-based degraders, enabling targeted proteasomal degradation of VCL without a classical CRBN degron motif. |
High-throughput proteomics + ubiquitinomics (DIA-MS), 100-compound CRBN-ligand screen across cancer cell lines |
bioRxiv (preprint)preprint |
Medium |
bio_10.1101_2024.10.18.618633
|
| 2024 |
RBM10 loss causes exon inclusion in VCL pre-mRNA; knockdown of the VCL exon-inclusion isoform in RBM10-null cells reduces cell velocity, while combined knockdown of VCL, CD44, and TNC exon-inclusion isoforms reverses metastasis in HrasG12V/Rbm10-KO mouse thyrocytes, demonstrating a specific pro-migratory function of the VCL exon-inclusion isoform. |
RNA-seq, isoform-specific siRNA knockdown, cell velocity assay, mouse Hras/Rbm10 KO tumor model, CRISPR screen |
bioRxiv (preprint)preprint |
Medium |
bio_10.1101_2024.07.09.602730
|
| 2025 |
In Ccm1-deficient zebrafish, endothelial vinculin displays excessive mechanically active focal adhesions in vivo. Genetic deletion of Talin1 to decouple focal adhesions demonstrates that the integrin β1–Talin1 complex acts independently of or downstream of KLF2/4 to drive endothelial cell enlargement and vascular malformation in CCM1-deficiency, repositioning vinculin-associated focal adhesion signaling in CCM pathogenesis. |
Live imaging of vinculin in ccm1 zebrafish mutants, Talin1 genetic deletion, CCM1-KO endothelial cells, force redistribution measurements |
bioRxiv (preprint)preprint |
Medium |
bio_10.1101_2025.11.25.688491
|
| 2024 |
Vinculin phosphorylation at tyrosine 822 (pY822) correlates with dynamic junction remodeling in the developing mouse heart and is lost as junctions mature postnatally. Homozygous Y822F knock-in mice develop cardiac dysfunction by 28 weeks; Y822F hearts show reduced vinculin and adherens junction proteins at cardiomyocyte junctions and increased α5/β1 integrin and fibronectin along lateral borders, demonstrating that pY822 regulates the balance between cadherin-based and integrin-based adhesion organization in cardiomyocytes. |
Y822F knock-in mouse model, cardiac function assessment (echocardiography), immunofluorescence quantification of junction proteins, biochemical fractionation |
bioRxiv (preprint)preprint |
Medium |
bio_10.1101_2024.10.28.620745
|
| 2024 |
Molecular dynamics simulations with enhanced sampling reveal that vinculin forms a catch bond with F-actin: force application increases bond lifetime, and this behavior is direction-dependent. Force shifts vinculin between weakly- and strongly-bound states, with both states having intrinsic catch bonding character; directional force promotes one state over the other, providing mechanistic insight into vinculin's role in mechanotransduction at focal adhesions. |
All-atom molecular dynamics simulation with enhanced sampling; comparison of predicted unbinding times with single-molecule experimental data |
bioRxiv (preprint)preprint |
Medium |
bio_10.1101_2024.10.10.617580
|
| 2025 |
Integrating FRET-based vinculin tension sensors (VinTS) with traction force microscopy reveals that at the cell level, vinculin tension and cellular tractions both increase with substrate stiffness. At the focal adhesion level, vinculin tension correlates with vinculin density while tractions scale with FA area and total vinculin content. Sub-FA analysis shows tension and traction both increase toward the cell periphery, establishing a multiscale mechanotransduction framework for vinculin. |
FRET vinculin tension sensor (VinTS), traction force microscopy (TFM), sub-FA spatial analysis |
bioRxiv (preprint)preprint |
Medium |
bio_10.1101_2025.01.09.632081
|