-
Cell Motility and the Cytoskeleton 1990Vinculin is clearly a key element in the transmembrane assemblages that link cells to each other or to the substrate. However, despite all the studies that have been... (Review)
Review
Vinculin is clearly a key element in the transmembrane assemblages that link cells to each other or to the substrate. However, despite all the studies that have been done on the protein, we still do not know its function within these assemblages. The bulk of the biochemical and cell biological evidence suggests that, in some unknown way, its presence in the junctions may be involved in the stable association of actin with the membrane, yet vinculin by itself does not appear to interact with actin. In the future, identification of additional junctional molecules that interconnect actin and vinculin may resolve this dilemma. Alternatively, studies with vinculin that is phosphorylated or acylated may yield clues to its function. Perhaps the complexity of the protein composition of microfilament-containing junctions suggests that protein assemblages rather than individual proteins provide novel functions. As new proteins belonging to these junctions are discovered, it will be important to assess their interaction with already known components such as vinculin and to ask if the protein combination has a particular function.
Topics: Animals; Cytoskeletal Proteins; Humans; Vinculin
PubMed: 2112986
DOI: 10.1002/cm.970160102 -
Cellular and Molecular Life Sciences :... Aug 2017Vinculin was identified as a component of focal adhesions and adherens junctions nearly 40 years ago. Since that time, remarkable progress has been made in understanding... (Review)
Review
Vinculin was identified as a component of focal adhesions and adherens junctions nearly 40 years ago. Since that time, remarkable progress has been made in understanding its activation, regulation and function. Here we discuss 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. We also highlight the recent understanding of how vinculin responds to and transmits force at integrin- and cadherin-containing adhesion complexes to the cytoskeleton. Furthermore, we discuss roles of vinculin in binding to and rearranging the actin cytoskeleton.
Topics: Actin Cytoskeleton; Adherens Junctions; Animals; Cadherins; Cell Adhesion; Cell Movement; Focal Adhesions; Humans; Integrins; Mechanotransduction, Cellular; Models, Molecular; Protein Interaction Maps; Vinculin
PubMed: 28401269
DOI: 10.1007/s00018-017-2511-3 -
Nature Communications Jul 2023The talin-vinculin axis is a key mechanosensing component of cellular focal adhesions. How talin and vinculin respond to forces and regulate one another remains unclear....
The talin-vinculin axis is a key mechanosensing component of cellular focal adhesions. How talin and vinculin respond to forces and regulate one another remains unclear. By combining single-molecule magnetic tweezers experiments, Molecular Dynamics simulations, actin-bundling assays, and adhesion assembly experiments in live cells, we here describe a two-ways allosteric network within vinculin as a regulator of the talin-vinculin interaction. We directly observe a maturation process of vinculin upon talin binding, which reinforces the binding to talin at a rate of 0.03 s. This allosteric transition can compete with force-induced dissociation of vinculin from talin only at forces up to 10 pN. Mimicking the allosteric activation by mutation yields a vinculin molecule that bundles actin and localizes to focal adhesions in a force-independent manner. Hence, the allosteric switch confines talin-vinculin interactions and focal adhesion build-up to intermediate force levels. The 'allosteric vinculin mutant' is a valuable molecular tool to further dissect the mechanical and biochemical signalling circuits at focal adhesions and elsewhere.
Topics: Actins; Talin; Vinculin; Allosteric Regulation; Focal Adhesions; Protein Binding
PubMed: 37463895
DOI: 10.1038/s41467-023-39646-4 -
FEBS Letters Apr 2013Vinculin, and its splice variant metavinculin, are scaffolding proteins that localize to cellular adhesions. Vinculin is a key player in mediating cell adhesion,... (Review)
Review
Vinculin, and its splice variant metavinculin, are scaffolding proteins that localize to cellular adhesions. Vinculin is a key player in mediating cell adhesion, motility, and cellular response to force. In the past decade, a number of new studies have evaluated the importance of vinculin oligomers, especially in their role of bundling F-actin. Emerging evidence also suggests that vinculin oligomerization is important for vinculin's scaffolding function. Here we describe the latest findings on vinculin's interaction with F-actin and we clarify the different known vinculin oligomers. Differences in these functions between vinculin and metavinculin provide key insights to the structure and function of these oligomers, and should guide further studies.
Topics: Actin Cytoskeleton; Actins; Humans; Models, Molecular; Protein Binding; Protein Multimerization; Protein Structure, Tertiary; Vinculin
PubMed: 23466368
DOI: 10.1016/j.febslet.2013.02.042 -
Cell Biology International May 2013The focal adhesion protein, vinculin, is important for transmitting mechanical forces and orchestrating mechanical signalling events. Deregulation of vinculin results in... (Review)
Review
The focal adhesion protein, vinculin, is important for transmitting mechanical forces and orchestrating mechanical signalling events. Deregulation of vinculin results in altered cell adhesion, contractility, motility and growth, all of which are important processes in cancer metastasis. This review summarises recent reports on the role of vinculin in cellular force generation and signalling, and discusses implications for a role of vinculin in promoting cancer cell migration in 3D environments.
Topics: Actins; Animals; Apoptosis; Carcinogenesis; Cell Adhesion; Cell Movement; Humans; Neoplasms; Signal Transduction; Vinculin
PubMed: 23494917
DOI: 10.1002/cbin.10064 -
Cell Biology International Mar 2016Cell-matrix adhesion and cell-cell contacts are essential for the metabolism, protein synthesis, survival, and cancer metastasis of cells. Major transmembrane receptors... (Review)
Review
Cell-matrix adhesion and cell-cell contacts are essential for the metabolism, protein synthesis, survival, and cancer metastasis of cells. Major transmembrane receptors are the integrins, which are responsible for cell-matrix adhesions, and the cadherins, which are important for cell-cell adhesions. Adherent cells anchor via focal adhesion proteins to the extracellular matrix, whereas cell-cell contacts connect via focal adherens junction proteins. The temporal formation of these connections is greatly strengthened either through externally applied stresses on the cell or by myosin-driven cell contractility. The mechanism by which protein(s) within these connections sense, transmit, and respond to mechanochemical signaling is currently strongly debated and various candidates have been named. Vinculin has been described as one of the key players in cell-matrix and cell-cell adhesions that build a strong physical connection for transmitting forces between the cytoskeleton, the extracellular matrix, and cell-cell connections.
Topics: Actins; Adherens Junctions; Cell Adhesion; Crk-Associated Substrate Protein; Extracellular Matrix; Humans; Integrins; Mechanotransduction, Cellular; Protein Binding; Vinculin
PubMed: 26909547
DOI: 10.1002/cbin.10563 -
Oncotarget Oct 2015
Topics: Animals; Cell Communication; Cell Membrane; Cell Movement; Focal Adhesions; Humans; Mice; Vinculin
PubMed: 26431280
DOI: 10.18632/oncotarget.5868 -
Cell Biology International Mar 2014Adherent cells, when mechanically stressed, show a wide range of responses including large-scale changes in their mechanical behaviour and gene expression pattern. This... (Review)
Review
Adherent cells, when mechanically stressed, show a wide range of responses including large-scale changes in their mechanical behaviour and gene expression pattern. This is in part facilitated by activating the focal adhesion (FA) protein p130Cas through force-induced conformational changes that lead to the phosphorylation by src family kinases. Janostiak et al. [Janostiak et al. Cell Mol Life Sci (2013) DOI 10.1007/s00018-013-1450-x] have reported that the phosphorylation site Y12 on the SH3 domain of p130Cas modulates the binding with vinculin, a prominent mechano-coupling protein in FAs. Tension changes in FAs (due to the anchorage of the SH3 domain and C-terminal) bring about an extension of the substrate domain of p130Cas by unmasking the phosphorylation sites. These observations demonstrate that vinculin is an important modulator of the p130Cas-mediated mechano-transduction pathway in cells. The central aim should be now to test that vinculin is critical for p130Cas incorporation into the focal adhesion complex and for transmitting forces to the p130Cas molecule.
Topics: Cell Adhesion; Crk-Associated Substrate Protein; Focal Adhesions; Humans; Mechanotransduction, Cellular; Phosphorylation; Vinculin
PubMed: 24497348
DOI: 10.1002/cbin.10204 -
European Heart Journal Jan 2023
Topics: Humans; Phosphorylation; Vinculin; Cardiovascular Diseases; Endothelial Cells; Permeability; Atherosclerosis
PubMed: 36514951
DOI: 10.1093/eurheartj/ehac704 -
Journal of Cell Science Jun 2023Vinculin is an actin-binding protein present at cell-matrix and cell-cell adhesions, which plays a critical role in bearing force experienced by cells and dissipating it...
Vinculin is an actin-binding protein present at cell-matrix and cell-cell adhesions, which plays a critical role in bearing force experienced by cells and dissipating it onto the cytoskeleton. Recently, we identified a key tyrosine residue, Y822, whose phosphorylation plays a critical role in force transmission at cell-cell adhesions. The role of Y822 in human cancer remains unknown, even though Y822 is mutated to Y822C in uterine cancers. Here, we investigated the effect of this amino acid substitution and that of a phosphodeficient Y822F vinculin in cancer cells. We observed that the presence of the Y822C mutation led to cells that proliferate and migrate more rapidly and contained smaller focal adhesions when compared to cells with wild-type vinculin. In contrast, the presence of the Y822F mutation led to highly spread cells with larger focal adhesions and increased contractility. Furthermore, we provide evidence that Y822C vinculin forms a disulfide bond with paxillin, accounting for some of the elevated phosphorylated paxillin recruitment. Taken together, these data suggest that vinculin Y822 modulates the recruitment of ligands.
Topics: Humans; Vinculin; Paxillin; Ligands; Cell Adhesion; Cell Communication; Focal Adhesions
PubMed: 37248996
DOI: 10.1242/jcs.260104