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Human Vinculin Protein expressed in HEK-293 Cells - ABIN2735299
Beppu, Sawai, Satoh, Mori, Kazami, Misawa, Shibuya, Ishibashi, Sogawa, Kado, Kodera, Nomura, Kuwabara: Autoantibodies against vinculin in patients with chronic inflammatory demyelinating polyneuropathy. in Journal of neuroimmunology 2015
Vinculin is necessary to maintain the integrity of the glomerular filtration barrier by modulating podocyte foot processes and stabilizing intercellular junctions.
ERalpha upregulates vinculin expression in breast cancer cells; Loss of vinculin promotes amoeboid features of cancer cells
We report that polyoma small T antigen leads to upregulation of tubulin and vinculin in a time dependent manner with tubulin expression being most significantly affected.
Differential phosphatidylinositol 4,5-diphosphate binding of vinculin isoforms promotes quasi-equivalent dimerization.
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, and to allow hMSCs branching. Another module involves paxillin and FAK, 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 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 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-vinculin binding interface using a combination of flexible docking and molecular dynamics simulations, and confirmed that the MAPK1-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 binding toward open vinculin.
These results suggest that vinculin promotes the nuclear localization of transcription factor TAZ 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, MYO5B and VCL, and mutations in these genes were exclusively found in malignant sympathetic paraganglioma tumors.
roles and mechanisms of phospholipids in regulating the structure and function of vinculin and of its muscle-specific metavinculin splice variant.
Upon actin engagement, the N-terminal "strap" and helix 1 are displaced from the vinculin tail helical bundle to mediate actin bundling.
This study defined a plastic relationship between vinculin-mediated tension and adhesion complex area that controls fundamental cell-matrix adhesion properties.
Analysis showed that ITGB4 and VCL were upregulated in exosomes derived from taxane-resistant prostate cancer cells suggesting them as useful markers for progression of prostate cancer associated with taxane-resistance.
vinculin, present in the joints of anti-citrullinated protein antibody (ACPA)(+) rheumatoid arthritis patients, was identified as an autoantigen targeted by ACPA and CD4(+) T cells.
The activation of vinculin by stretched talin induces a positive feedback that reinforces the actin-talin-vinculin association.
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 and vinculin form a molecular apparatus that generates cohesive cell-cell contacts in cultured mammalian epithelia.
Vinculin-M94I resulted in 37% reduction in peak sodium current compared to wild type and the combination of Vinculin-M94I and pH 7.0 decreased peak sodium current.
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.
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 remodeling in complex 3D environments by increasing cell-ECM adhesion and traction force generation.
Force-dependent conformational switch of alpha-catenin controls vinculin binding.
Mutant vinculin expressing cells are altered in cell migration, which is accompanied by changes in cell adhesion.
show that Src phosphorylation of Y1065 within the C-terminal hairpin regulates Vt-mediated actin bundling and provide a detailed characterization of vinculin Y1065 mutations
The E29R mutation might prime the vinculin head for F-actin binding, which results in higher cell stiffness, contractile force, and strengthening of focal adhesions.
Vcl plays a crucial role in stabilizing gap junctions and myocyte integrity through direct interactions with ZO-1 and stabilization of CX43.
serine phosphorylation is required for the activation of vinculin and force transmission in focal adhesions.
VCL binding talin, but not Arp2/3, is critical for osteoclast function, and its selective inhibition retards physiological bone loss.
Crk-associated substrate -vinculin binding significantly affects the dynamics of Crk-associated substrate and vinculin within focal adhesions as well as the size of focal adhesions.
This study demonistrated that Deletion of the vinculin disturbs the localization of GFAP in Bergmann glial cells in mice.
These results identify vinculin as a major controller of integrin-mediated adhesion dynamics in B cells
role for vinculin in ventricular myocyte mechanics and dysfunction
These findings demonstrate the crucial importance of the tight control of the activity of vinculin.
Syndecan-4 acts as a central mediator that bridges fibronectin, integrin and intracellular components (actin and vinculin) and once silenced, the cytoskeleton protein network is disrupted, highlighting Syn4 relevance for balanced cell behavior.
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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