Vinculin

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Vinculin

Existing structural data : 1tr2

Properties of human protein
Mass / length primary structure 1133 amino acids
Isoforms 3
Identifier
Gene name VCL
External IDs
Occurrence
Parent taxon multicellular animals

Vinculin (from the Latin . 'Vinculum' for ankle) is a 116  kDa large protein that is found in almost all cells of animals. It binds actin , a structural protein , and is part of cell-cell connections , the so-called adherens junctions, and also of cell-extracellular contacts, which are grouped together in the group of focal adhesions .

There it is the main structural protein, i.e. H. it mainly has functions in the structure and connection of proteins and cells but not in metabolism. It was first found in smooth muscle cells and has since been found in most other mammalian cell types.

When people can mutations in the VCL - gene to Vinculinmangel and this to dilated cardiomyopathy lead type I.

It was discovered independently by Benny Geiger and Keith Burridge in 1979.

structure

Interactions of structural proteins at an adherens junction

General:

  • Vinculin can be thought of as a three-part protein: head - connecting part - tail
  • In the connecting part there are binding sites for other proteins; d. H. other proteins can "dock" there
  • Proteins that can bind to vinculin are e.g. B. talin, catenins , actin , paxillin.
  • The head and tail of vinculin can loosely connect to each other and make the areas in the connecting part inaccessible to other proteins.

In detail:

Vinculin has a globular head that is connected to the end domain by means of a proline-rich region. There are numerous binding sites for other proteins in all regions of the protein. The binding site of the talin, which apparently couples parts of the β-integrin with the actin network and is thus responsible for integrin activation and focal adhesion assembly, was best characterized .

Interestingly, the head and tail of the vinculin can associate with each other and thus mask a number of binding sites. An active vinculin may consist of dissociated domains and thus freely usable binding sites, although other conformations are probably also possible.

Functions

General brief overview:

  • Vinculin is a structural protein and is mainly used by cells to establish cell contacts and cell-matrix contacts.
  • Vinculin acts as a tumor suppressor , i.e. H. the lack of protein can promote the development of tumors
  • Vinculin apparently has a function in the initiation of programmed cell death ( apoptosis )
  • Vinculin influences the structure of the actin cytoskeleton (the supporting framework of the cell)
  • Vinculin can protect other proteins from degradation and thus acts as a tumor suppressor

In detail:

The exact role that vinculin plays in “ focal adhesions ” is still unclear. Vinculin overexpression reduces cell movement, whereas vinculin inhibition stimulates cell movement. Cells without vinculin (vinculin KOs) are less adherent, less spread out, more mobile and have smaller and fewer "focal adhesions" than normal cells.

In addition, the activity of such proteins as FAK (focal adhesion kinase) and paxillin is increased, which is typical for mobile cells. Vinculin is also a tumor suppressor .

Apparently, vinculin also has functions in the apoptosis signaling pathway, because cells of a vinculin knockout mouse are resistant to apoptosis.

Although vinculin is mainly found in cadherin- mediated cell-cell connections (" adherens junctions "), it is not necessary to establish these connections. However, defects were found in the tight junctions of the vinculin-KO cells.

It was assumed that vinculin the mechanical connections between the protein complexes (consisting of E-cadherin, beta- catenin , alpha-catenin) and the Aktinnetz strengthens. However, this theory is being challenged by recent studies.

Apparently there is only a loose connection between the actin cytoskeleton and the cell-cell connections, so that the role of vinculin is still unclear. However, new data show the impact on actin assembly and modification.

It is also noteworthy that KO cells that no longer have vinculin do not express PTEN (a lipid phosphatase). Apparently, vinculin can stop the degradation of PTENs, since the amount of mRNA is unchanged from that in normal cells. PTEN is one of the most frequently mutated tumor suppressor genes . There are tumors in which no mutations were found but the PTEN was still not present. Here it is possible that vinculin mutations do not prevent the breakdown of the PTEN and thus promote tumor development.

Individual evidence

  1. ↑ Homologues at OMA
  2. ^ Ziegler, et al .: The structure and regulation of vinculin. Trends in Cell Biology Vol.16 No.9 453ff, 2009 PMID 16893648
  3. ↑ JOCKUSCH, BM et al .: The molecular architecture of focal adhesions. (1995) Annu. Rev. Cell Dev. Biol. 11, 379-416 PMID 8689563
  4. ↑ UniProt P18206
  5. ^ Geiger, A 130K protein from chicken gizzard: its localization at the termini of microfilament bundles in cultured chicken cells. Cell, Vol. 18, 1979, pp. 193-205, PMID 574428
  6. ↑ K. Burridge, JR Feramisco: Microinjection and localization of a 130K protein in living fibroblasts: a relationship to actin and fibronectin, Cell, Volume 19, 1980, pp. 587-95. PMID 6988083 .
  7. ^ Critchley, DR (2000) Focal adhesions - the cytoskeletal connection. Curr. Opin. Cell Biol. 12, 133-139
  8. ↑ Johnson, RP and Craig, SW (1994) An intramolecular association between the head and tail domains of vinculin modulates talin binding. J. Biol. Chem. 269, 12611-12619
  9. ↑ Xu, W. et al. (1998) Vinculin knockout results in heart and brain defects during embryonic development. Development 125, 327-337
  10. ↑ Rodriguez Fernandez, JL et al. (1992) Suppression of tumorigenicity in transformed cells after transfection with vinculin cDNA. J. Cell Biol. 119, 427-438
  11. ↑ Coll, JL et al. (1995) Targeted disruption of vinculin genes in F9 and embryonic stem cells changes cell morphology, adhesion, and locomotion. Proc. Natl. Acad. Sci. USA 92, 9161-9165
  12. ↑ Watabe-Uchida, M. et al. (1998) alpha-catenin-vinculin interaction functions to organize the apical junctional complex in epithelial cells. J. Cell Biol. 142, 847-857
  13. ↑ Yamada, S. et al. (2005) Deconstructing the cadherin-catenin-actin complex. Cell 123, 889-90
  14. ↑ Wen KK, Rubenstein PA, DeMali KA. J Biol Chem. 2009 Oct 30; 284 (44): 30463-73 Vinculin nucleates actin polymerization and modifies actin filament structure
  15. ↑ Subauste, MC et al. (2005) Vinculin controls PTEN protein level by maintaining the interaction of the adherens junction protein betacatenin with the scaffolding protein MAGI-2. J. Biol. Chem. 280, 5676-5681

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