Vinculin - Mechanism and Function

Mechanism and Function

Background

Cell spreading and movement occur though the process of binding of cell surface integrin receptors to extracellular matrix adhesion molecules. Vinculin is associated with focal adhesion and adherens junctions, which are complexes that nucleate actin filaments and crosslinkers between the external medium, plasma membrane, and actin cytoskeleton(Xu et al. 1998). The complex at the focal adhesions consists of several proteins such as vinculin, α-actin, paxillin, and talin, at the intracellular face of the plasma membrane.

In more specific terms, the amino-terminal of vinculin binds to talin, which, in turn, binds to β-integrins, and the carboxy-terminal binds to actin, phospholipids, and paxillin-forming homodimers. The binding of vinculin to talin and actin is regulated by polyphosphoinositides and inhibited by acidic phospholipids. The complex then serves to anchor actin filaments to the membrane(Ezzell et al. 1997).

The loss of vinculin impacts a variety of cell functions; it disrupts the formation of the complex, and prevents cell adhesion and spreading. The absence of the protein demonstrates a decrease in spreading of cells, accompanied by reduced stress fiber formation, formation of fewer focal adhesions, and inhibition of lamellipodia extension (Goldman et al. 2001). It was discovered that cells that are deficient in vinculin have growth cones that advance more slowly, as well as filopodia and lamellipoida that were less stable than the wild-type. Based on research, it has been postulated that the lack of vinculin may decrease cell adhesion by inhibiting focal adhesion assembly and preventing actin polymerization. On the other hand, overexpression of vinculin may restore adhesion and spreading by promoting recruitment of cytoskeletal proteins to the focal adhesion complex at the site of integrin binding(Ezzell et al. 1997). Vinculin's ability to interact with integrins to the cytoskeleton at the focal adhesion appears to be critical for control of cytoskeletal mechanics, cell spreading, and lamellipodia formation. Thus, vinculin appears to play a key role in shape control based on its ability to modulate focal adhesion structure and function.