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Study used an all-heavy-atom structure-based model to study vinculin activation by talin in a high-tension context mechanically driven by F-actin, showed that vinculin activation may proceed from an intermediate state stabilized by partial talin-vinculin association. There is a low-force regime and a high-force regime where vinculin activation is dominated by two different pathways with distinct responses to force.
Vinculin head-tail interaction is required on soft substrates to destabilize vinculin and talin in FAs (zeige FAS ELISA Kits), and to allow hMSCs branching. Another module involves paxillin (zeige PXN ELISA Kits) and FAK (zeige PTK2 ELISA Kits), which soft substrates also destabilize, but independently of vinculin head-tail interaction. This multi-modularity may be key to allow a versatile response to complex biomechanical cues.
The central role of talin and vinculin in cell adhesions suggests that the disintegration of the tissue in atherosclerosis could be partially driven by downregulation of these genes, leading to loosening of cell-ECM (zeige MMRN1 ELISA Kits) interactions and remodeling of the tissue.
East Asian common VCL variant p.Asp841His (D841H) was associated with sudden unexplained nocturnal death syndrome (SUNDS) in the Chinese Han population.
We identified mutations in VCL associated with Short segment Hirschsprung disease. Correction of this mutation in induced pluripotent stem cells using CRISPR/Cas9 editing, as well as the RET (zeige RET ELISA Kits) G731del mutation that causes Hirschsprung disease with total colonic aganglionosis, restored enteric neural crest cell function.
This review discusses the current understanding of the roles of vinculin in cell-cell and cell-matrix adhesions. Emphasis is placed on the how vinculin is recruited, activated and regulated. [review]
Study predicted the structure of the MAPK1 (zeige MAPK3 ELISA Kits)-vinculin binding interface using a combination of flexible docking and molecular dynamics simulations, and confirmed that the MAPK1 (zeige MAPK3 ELISA Kits)-vinculin interaction is mechanically regulated, and implicated a change in the vinculin D3-D4 cleft size upon vinculin activation as the basis for the conformational selectivity of MAPK1 (zeige MAPK3 ELISA Kits) binding toward open vinculin.
These results suggest that vinculin promotes the nuclear localization of transcription factor TAZ (zeige TAZ ELISA Kits) to inhibit the adipocyte differentiation on rigid extracellular matrix.
The VCL-encoding protein was involved in cardiomyopathy that associated with hypertension, therefore our results suggest the rs4746172 of VCL may be a novel target for clinical interventions to reduce CVD risk by regulating blood pressure in male Chinese
Three novel genes were identified as recurrently mutated; MYCN (zeige MYCN ELISA Kits), MYO5B and VCL, and mutations in these genes were exclusively found in malignant sympathetic paraganglioma tumors.
Study show that zebrafish contain two homologous vinculin isoforms, of which the sequence of key functional domains is conserved with several higher vertebrate. Loss of both zygotic vcla and maternal contribution of vcla did not result in notable defects, while the additional loss of zygotic vclb is lethal only after embryonic stages. These data indicate that embryonic development in zebrafish can occur without vinculin.
Results suggest that myosin VI (zeige MYO6 ELISA Kits) and vinculin form a molecular apparatus that generates cohesive cell-cell contacts in cultured mammalian epithelia.
Lipid binding increases vinculin activation and turnover at focal adhesions.
results suggest that the vinculin-actin interaction participates in FA-mediated mechanotransduction
The results indicate that lipid rafts play an important role in extracellular matrix stiffness regulation of cell migration via expression vinculin and its interaction with vinexin alpha (zeige Sorbs3 ELISA Kits).
Binding of vinculin to the R1-R3 region of the talin rod is important for focal adhesion stability.
These data demonstrate that Src-mediated phosphorylation is necessary for vinculin activation, and that phosphorylation controls cytoskeletal mechanics by regulating force transmission between the actin cytoskeleton and focal adhesion proteins.
results suggest that vinculin promotes directionally persistent cell migration and tension-dependent ECM (zeige MMRN1 ELISA Kits) remodeling in complex 3D environments by increasing cell-ECM (zeige MMRN1 ELISA Kits) adhesion and traction force generation.
Force-dependent conformational switch of alpha-catenin (zeige CTNNA1 ELISA Kits) controls vinculin binding.
Mutant vinculin expressing cells are altered in cell migration, which is accompanied by changes in cell adhesion.
show that Src (zeige SRC ELISA Kits) phosphorylation of Y1065 within the C-terminal hairpin regulates Vt-mediated actin bundling and provide a detailed characterization of vinculin Y1065 mutations
These findings demonstrate the crucial importance of the tight control of the activity of vinculin.
Vinculin is a cytoskeletal protein associated with cell-cell and cell-matrix junctions, where it is thought to function as one of several interacting proteins involved in anchoring F-actin to the membrane. Defects in VCL are the cause of cardiomyopathy dilated type 1W. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Multiple alternatively spliced transcript variants have been found for this gene, but the biological validity of some variants has not been determined.
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