Vinculin Family

Aliases: Metavinculin, vinculin, VCL, RP11-178G16.3, CMD1W, MVCL

Processes & Diseases

Processes involved: adhesion

Pfam Domain Structure

From VCL (human) - phosphorylation sites added via direct mapping

Members of the Vinculin Family
1: VCL » Human Mouse Rat Chicken Fly Worm
CMKB VCL Vcl Vcl VCL - -
Entrez Gene 7414 22330 305679 396422 - -
Uniprot VINC_HUMAN VINC_MOUSE VINC_RAT VINC_CHICK - -
OMIM 193065 - - - - -
Reagents - 4 available - 3 available - -
Results 4 available 2 available - - - -
Family Summary

Vinculin is a 117 kDa protein localized to focal adhesions. The globular head region of vinculin (Vh) contains the binding sites for talin and alpha-actinin whereas its rod-like tail domain (Vt) contains the binding sites for F-actin and paxillin. The proline-rich region between Vh and Vt interacts with VASP. The intramolecular interaction between Vh and Vt renders these sites inaccessible to vinculin binding partners. The crystal structure of Vt features a bundle of five amphipathic helices and a C-terminal arm, which emerges as a hydrophobic hairpin surrounded by a collar of basic residues. The crystal structure of Vt leads to a regulation model in which an interaction between the negatively charged head groups of phospholipids and the basic collar of Vt disrupts the intramolecular interaction of vinculin and thus exposes multiple protein binding sites. Unlike talin, vinculin is not essential for focal adhesion assembly in that vinculin-null ES (embryonic stem) cells still form focal adhesion-like structures. Vinculin may carry out its function by stabilizing the interaction between talin and actin (and/or the interaction between talin and membrane) or by recruiting profilin/G-actin to actin polymerization sites.

References
  1. Bakolitsa C, Cohen DM, Bankston LA, Bobkov AA, Cadwell GW, Jennings L, Critchley DR, Craig SW, Liddington RC. Structural basis for vinculin activation at sites of cell adhesion Nature 2004 430:583-6 (PubMed)
  2. Bois PR, O'Hara BP, Nietlispach D, Kirkpatrick J, Izard T. The vinculin binding sites of talin and alpha-actinin are sufficient to activate vinculin J. Biol. Chem. 2006 281:7228-36 (PubMed)
  3. Burridge K, Mangeat P. An interaction between vinculin and talin Nature 1984 308:744-6 (PubMed)
  4. Critchley DR. Cytoskeletal proteins talin and vinculin in integrin-mediated adhesion Biochem. Soc. Trans. 2004 32:831-6 (PubMed)
  5. del Rio A, Perez-Jimenez R, Liu R, Roca-Cusachs P, Fernandez JM, Sheetz MP. Stretching single talin rod molecules activates vinculin binding Science 2009 323:638-41 (PubMed)
  6. Gilmore AP, Burridge K. Regulation of vinculin binding to talin and actin by phosphatidyl-inositol-4-5-bisphosphate Nature 1996 381:531-5 (PubMed)
  7. Grashoff C, Hoffman BD, Brenner MD, Zhou R, Parsons M, Yang MT, McLean MA, Sligar SG, Chen CS, Ha T, Schwartz MA. Measuring mechanical tension across vinculin reveals regulation of focal adhesion dynamics Nature 2010 466:263-6 (PubMed)
  8. Le Clainche C, Carlier MF. Regulation of actin assembly associated with protrusion and adhesion in cell migration Physiol. Rev. 2008 88:489-513 (PubMed)
  9. Mierke CT, Kollmannsberger P, Zitterbart DP, Diez G, Koch TM, Marg S, Ziegler WH, Goldmann WH, Fabry B. Vinculin facilitates cell invasion into three-dimensional collagen matrices J. Biol. Chem. 2010 285:13121-30 (PubMed)
  10. Nayal A, Webb DJ, Horwitz AF. Talin: an emerging focal point of adhesion dynamics Curr. Opin. Cell Biol. 2004 16:94-8 (PubMed)
  11. Spinardi L, Marchisio PC. Podosomes as smart regulators of cellular adhesion Eur. J. Cell Biol. 2006 85:191-4 (PubMed)
  12. Ziegler WH, Liddington RC, Critchley DR. The structure and regulation of vinculin Trends Cell Biol. 2006 16:453-60 (PubMed)
Consortium Results & Data
Results & Data
Ortholog Species Type Description Method Status Source Publications
VCL none phosphorylation site Vinculin Ectopic expression in HEK cells 2 phospho-sites in 92.1% coverage of 1062 aa Parsons
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VCL none structure Alpha-actinin / beta1-integrin - Vinculin 1-258 complex 2D crystallization on lipid monolayers none Taylor Kelly et al.
VCL none structure Vinculin (full length) X-Ray crystallography completed Liddington Bakolitsa et al., Bakolitsa et al., Saunders et al., Ziegler et al.
VCL none structure Meta-vinculin C-terminal domain X-Ray crystallography, NMR completed Liddington Bakolitsa et al.
VCL none structure Vinculin-tail actin EM, tomography and docking completed Hanein Janssen et al.
Discovery» siRNA migration screen using a wound healing approach
Gene Description     MCF-10A phenotype     Secondary screen Wound Image Morphology Time-lapse
VCL
Aliases: MVCL
Entrez Gene: 7414
siRNA catalog
vinculin
mRNA: NM_003373
Library: MAR
Classification: cytoskeletal
Focal Adhesion Related: Yes
Final bin: Discordant
SMARTpool bin: No change
Avg area: 1.34
Avg Alamar: 0.97
Knockdown %: not done
  VCL
Link
VCL
Link
 
Discovery» siRNA Focal Adhesion Phenotypes
Gene Description High-Res Montage
VCL
Aliases: MVCL
Entrez Gene: 7414
siRNA catalog
vinculin
mRNA: NM_003373
Library: MAR
VCL
Link
VCL
Link
Proteomics» Table 1. Identification and Quantitation of Proteins from Cell Body (CB) and Pseudopodium (PD) fractions
IPI Locus Description CB Spectra CB peptide PD Spectra PD peptide ratio
IPI00291175 VCL VINCULIN ISOFORM VCL . 94 34 156 45 1.66
Proteomics» Table 2. Proteins in major organelles and subcellular compartments
IPI Locus Description CB Spectra PD Spectra ratio Location
IPI00291175 VCL VINCULIN ISOFORM VCL . 94 156 1.66 cytoskeleton
Discovery» MTLn3 invasive data
Gene mRNA Description Expression Ratio
Vcl
Entrez Gene: 22330
mRNA: AA275245
UniGene: Mm.279361
Vinculin 2.2
Discovery» PyMT invasive data
Gene mRNA Description Expression Ratio
Vcl
Entrez Gene: 22330
mRNA: AA275245
UniGene: Mm.279361
Vinculin 18.06
Consortium Related Products*
Mice » activity page
Ortholog Species Name Method Phenotype Status Jax Availability Comments Source Publications
VCL mouse Vinculin
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Death by E10, with embryos displaying 30-40% reduction in size, lack of midline fusion of the rostral neural tube and developmental defects in heart, somites and limbs. completed
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Xu et al.
VCL mouse Vinculin - F9 embryonal carcinoma cells
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Normal adherence to fibronectin, reduced spreading, increased amounts of alpha-actinin, talin and paxillin at focal adhesions. completed
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Volberg et al.
VCL mouse Vinculin - F9 embryonal carcinoma cells
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Altered cell morphology and motility. Absence of stress fibers. completed
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Goldmann et al.
VCL mouse Vinculin - embryonic fibroblasts
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Reduced adhesion to fibronectin, vitronectin, laminin and collagen and increased migration rates over these substrates. completed
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Xu et al.
Constructs » activity page
Ortholog Species Targets Name Amino Acid Range Portion Protocol Source
VCL chicken Vinculin pET15b-VD1 1-258 Vinculin Head domain (Y100E mutant)
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Liddington
VCL chicken Vinculin pET15b-VD1 1-258 Vinculin -head domain 1
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Liddington
VCL chicken Vinculin pET15b-VD1 879-1066 Vinculin Tail (Y1064E mutant)
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Liddington
Biosensors » activity page
Ortholog Species Name Type Comments Source Publications
VCL none Vinculin - Insertion of a FRET pair in vinculin Intramolecular FRET between FPs - Insertion of a FRET pair in vinculin compiled by CMC
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Chen et al.

* The resources presented here are largely those generated by the Consortium. The sidebar provides public databases that complement Consortium activities. For mice and biosensors, a public database is not available and therefore we have attempted to generate a migration related list for your convenience.

The primary classification of CMKB families is the homeomorphic family, whose members are both homologous (evolved from a common ancestor) and homeomorphic (sharing full-length sequence similarity and a common domain architecture).