Focal adhesion

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Immunofluorescence staining of the actin cytoskeleton (green) and the focal adhesion protein vinculin (red) in a fibroblast cell. The adhesion sites can be seen as red spots at the ends of the actin bundles.

Focal adhesions (engl. Focal adhesion ), and focal contacts mentioned are anchored cell connections that the actin - cytoskeleton of a cell mechanically to the substrate ( extracellular matrix , in short: ECM ) couple. They are limited to clearly delimited areas of the cell where the plasma membrane reaches up to 15 nm of the substrate. Focal adhesions can be composed of over 50 different proteins , which suggests a considerable range of functions.

In fact, they not only serve to anchor the cell, but also act as signal transmitters that inform the cell about the state of the ECM and thus influence its behavior. In sessile cells, focal adhesions are normally quite stable, while in migrating cells they are briefly built up and broken down. This plays an important role for the immune defense , for example , in which leukocytes perform a decelerating rolling movement along the vascular endothelium and finally migrate into inflamed tissue .

construction

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

Adhesion dynamics in migrating cells

The dynamic build-up and breakdown of focal adhesions plays a central role , especially in cell migration . In migrating cells, the protein composition and morphology of focal contacts change in the course of their existence, which is why they can be divided into different types. Early adhesions occur when the lamellipodium is advanced ( protrusion ) near the cell front and are called focal complexes. They are quite small ( 0.25μm ² ) and contain, in addition to α₅β₃ integrin, other proteins such as talin, paxilin and phosphotyrosin. Most Fokalkomplexe dissolve during retraction of lamellipodium ( retraction on again). The remainder enlarge and mature into stable focal adhesions by adding other proteins such as B. Recruit Zyxin. Focal adhesions move very little relative to the substrate, so that the cell migrates over them in the course of migration. The adhesion sites therefore move from front to back relative to the cell.

At the rear end of the cell, the focal adhesions must be dissolved in order to allow the cell body to retract. The mechanism of this so-called rear detachment is still poorly understood and is likely to take place in different ways. The separation of the connection between the actin cytoskeleton and the substrate can in principle take place purely mechanically by cellular contact forces or biochemically. It could be shown that the inhibition of so-called calpain - proteases leads to the stabilization of focal adhesions and reduces the substrate detachment. Since some proteins of focal adhesions belong to the substrates of calpain, it could be that these are specifically degraded in the course of the rear detachment .

Function as a mechanosensor

Mechanical forces exerted on focal adhesions can activate the intracellular signaling protein Src and cause the adhesions to grow. This indicates that focal adhesions act as mechanosensors and suggests that myosin-mediated tensile forces may contribute to the maturation of the focal complexes.

literature

  • B. Alberts et al: Molecular Biology of the Cell. 4th edition. Garland Science, 2002, ISBN 0-8153-4072-9 .

swell

  1. ↑ a b R. Zaidel-Bar, M. Cohen, L. Addadi, B. Geiger: Hierarchical assembly of cell-matrix adhesion complexes. In: Biochemical Society Transactions . 32, 2004, pp. 416-420.
  2. ^ A b E. Zamir, B. Geiger: Molecular complexity and dynamics of cell-matrix adhesions. In: Journal of Cell Science. 114, 2001, pp. 3583-3590.
  3. ↑ a b D. Riveline, E. Zamir, NQ Balaban, US Black, T. Ishizakid, p Narumiyad, Z. Kamb, B. Geiger, AD Bershadsky: Focal contacts as mechanosensors: Applied externally local mechanical force induces growth of focal contacts by an mDia1-dependent and ROCK-independent mechanism. In: Journal of Cell Biology . 153 (6), 2001, pp. 1175-1186.
  4. ↑ A. Huttenlocher , SP Palecek, Q. Lu, W. Zhang, RL Mellgren, DA Lauffenburger, MH Ginsberg, AF Horwitz: Regulation of cell migration by the calcium-dependent protease calpain. In: Journal of Biological Chemistry . 272, 1997, pp. 32719-32722.
  5. ↑ Y. Wang, EL Botvinick, Y. Zhao, MW Berns, S. Usami, RY Tsien , S. Chien: Visualizing the mechanical activation of Src. In: Nature . 434, 2005, pp. 1040-1045.

See also

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