Vinculin

• OMIM: 193 065
• UniProt: P18206

Vinculin is a 116 kDa protein that is found in almost all cells of animals. It binds actin, a structural protein, and is a component of cell - cell junctions, adherens junctions, and also the so-called cell - extracellular contacts that are combined in the group of focal adhesions.

There is the main structural protein, i.e., it functions mainly in the structure and the combination of proteins and cells, but not in the metabolism. It was first found in smooth muscle and has since been detected in the majority of other types of cells of mammals.

In humans, mutations in the gene for VCL Vinculinmangel and run this to dilated cardiomyopathy type I.

Structure

General:

• Vinculin can be thought of as a three-part protein: head - to-tail connection part

• In connection part are binding sites for other proteins; that is, there can "dock" other proteins

• Proteins that are able to bind to, for example, talin, vinculin, catenins, actin, paxillin.

• Head and tail Vinculins can connect with each other loosely and make the points in the connector for other proteins inaccessible.

In detail:

Vinculin has a globular head which is connected by a proline-rich region with the Enddomäne. In all regions of the protein are numerous binding sites for other proteins. The best characterizes this case the binding site of the Talins which was apparently coupled parts of the beta- integrin with the Aktinnetz and so is responsible for integrin activation and " focal adhesion " assembly.

Interestingly, the head and the end of the Vinculins associate with each other and thus mask some binding sites. An active vinculin might consist of dissociated domains and so freely available binding sites, although probably other conformations are possible.

Functions

General short overview:

• Vinculin is a structural protein, and is mainly used by the cell for the establishment of cell contact and cell-matrix contacts.

• Vinculin acts as a tumor suppressor, that is, the absence of the protein may contribute to the development of tumors

• Vinculin apparently has a function in the induction of programmed cell death ( apoptosis)

• Vinculin affects the structure of the actin cytoskeleton ( the supporting structure of the cell)

• Vinculin can protect other proteins from degradation and acts as well as a tumor suppressor

In detail:

The exact role of vinculin in "focal adhesions " plays is still unclear. Vinculin overexpression reduced the cell movement, whereas the vinculin inhibition stimulates cell movement. Cells lacking vinculin ( vinculin KOs ) are less adherent, less spread, more flexible and have smaller and less "focal adhesions " than normal cells.

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

Vinculin apparently also has functions in the apoptosis signaling pathway, because the cells of a vinculin KO mouse are resistant to apoptosis.

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

It was assumed that the mechanical connections between the vinculin protein complexes (consisting of E -cadherin, beta- catenin, alpha- catenin ) and strengthens the Aktinnetz. This theory is, however, provided by recent studies in question.

Apparently there is only a loose connection of the actin cytoskeleton with the cell - cell junctions, so that the role Vinculins is still unclear. However, new data show the influence on the Aktinzusammenbau and modification.

It is also noteworthy that KO cells, which have no more vinculin, no express PTEN ( a lipid phosphatase ). Apparently, vinculin can stop the degradation PTENs because the mRNA abundance is unchanged to 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 that PTEN was still not present. Here it is possible that the degradation of PTEN is not prevented by vinculin mutations and thus tumor development is favored.