Focal adhesion

Focal adhesions (English focal adhesion ) are anchored cell connections that the actin cytoskeleton of a cell mechanically to the substrate ( Extracellular Matrix, in short: ECM) couple. You are limited to well-defined regions of the cell in which the plasma membrane comes close to the substrate down to 15 nm. Focal adhesions are composed of about 50 different proteins, suggesting a significant functional.

In fact, they not only serve to anchor the cell but act beyond as signal transducers that inform the cell about the state of the ECM and thus influence their behavior. In sessile cells Focal adhesions are normally quite stable, while they are in migrating cells briefly and dismantled. This example plays an important role for the immune system, perform a decelerating rolling motion in the leukocytes along the vascular endothelium, and finally migrate into inflamed tissue.

Construction

The contact with proteins of the ECM is primarily mediated via transmembrane integrins assemble into large protein clusters and their extracellular domain proteins with specific amino acid sequence ( RGD ) binding (eg, fibronectin, laminin, vitronectin or collagen). Integrins are heterodimers and are each composed of an α and a β subunit. These subunits are present in different isoforms which differ in their ability to bind to ECM proteins. The β - subunit is coupled to the intracellular side via adapter proteins (eg, talin, α - actinin, filamin, and vinculin ) to actin filaments. In addition to structuring proteins found in focal adhesion many signal-transducing proteins such as the tyrosine kinases c -Src or FAK ( focal adhesion kinase ).

Adhäsionsdynamik in migrating cells

The dynamic assembly and disassembly of focal adhesions plays a central role, especially in cell migration. In migrating cells, the protein composition and morphology of focal adhesions in the course of its existence, which is why they can be divided into different types of changes. Early adhesions arise during the advance of the lamellipodium (protrusion ) near the cell front and are called Fokalkomplexe. They are quite small ( 0.25μm ²) and, in addition α ₅ β ₃ integrin other proteins such as talin, Paxilin and phosphotyrosine. Most Fokalkomplexe dissolve during retraction of the lamellipodium ( retraction ) again. The remaining expand and mature into stable focal adhesions by recruiting other proteins such as zyxin. Focal adhesions move relative to the substrate is very little, so that the cell during migration across wanders about them. The adhesion sites, therefore, move relative to the cell from the front to the rear.

The rear end of the focal adhesion cell must be dissolved to allow the rounding of the cell body. The mechanism of this is the so-called rear detachment yet very little understood and probably takes place in various ways. The separation of the connection between the actin cytoskeleton and substrate can be done purely mechanically or biochemically by cellular Kontaktionskräfte principle. It has been shown that the inhibition of so-called calpain proteases for stabilization of focal adhesion leads, and reduces the substrate detachment. As to the substrates of calpain some proteins of focal adhesions are, it could be that these are degraded specifically in the course of the rear detachments.

Function as mechanosensor

Mechanical forces, which are exerted on focal adhesions, the intracellular signaling protein can activate Src and cause the growth of adhesions. This shows that focal adhesions act as mechanosensors, and points out that myosinvermittelte tensile forces could contribute to the maturation of the Fokalkomplexe.