Focal adhesion



 

In cell biology, focal adhesions (also cell-matrix adhesions or FAs) are specific types of large macromolecules that mediate the regulatory effects (e.g. cell anchorage) of extracellular matrix (ECM) adhesion on cell behavior.[1]

Focal adhesions serve as the mechanical linkages to the ECM, and as a biochemical signalling hub to concentrate and direct numerous signaling proteins at sites of integrin binding and clustering.  

Structure and function

Focal adhesions are large, dynamic protein complexes through which the cytoskeleton of a cell connects to the extracellular matrix, or ECM. They are limited to clearly defined ranges of the cell, at which the plasma membrane closes to within to 15nm of the ECM substrate.[2] Focal adhesions are in a state of constant flux: proteins associate and disassociate with it continually as signals are transmitted to other parts of the cell, relating to anything from cell motility to cell cycle. Focal adhesions can contain over 100 different proteins, which suggests a considerable functional diversity.[3] They actually serve for not only the anchorage of the cell, but can function beyond that as signal carriers (sensors), which inform the cell about the condition of the ECM and thus affect their behavior.[4] In sessile cells, focal adhesions are quite stable under normal conditions, while in moving cells their stability is diminished: this is because in motile cells, focal adhesions are being constantly assembled and disassembled as the cell establishes new contacts at the leading edge, and breaks old contacts at the trailing edge of the cell. One example of their important role is in the immune system, in which white blood cells migrate along the connective endothelium following cellular signals and to damaged biological tissue.

Morphology

Connection between focal adhesions and proteins of the extracellular matrix generally involves the protein vinculin. Many other intracellular signalling proteins, such as focal adhesion kinase, bind to and associate with this integrin-adapter protein-cytoskeleton complex, and this forms the basis of a focal adhesion.

Adhesion dynamics with migrating cells

The dynamic assembly and disassembly of focal adhesions plays a central role in cell migration. During cell migration, both the composition and the morphology of the focal adhesion changes. Initially, small (0.25μm²) focal adhesions called "focal complexes" are formed at the leading edge of the cell in calpain is involved: it has been shown that the inhibition of calpain leads to the inhibition of focal adhesion-ECM separation. Focal adhesion components are amongst the known calpain substrates, and it is possible that calpain degrades these components to aid in focal adhesion disassembly[5]

Natural biomechanical sensor

Extracellular mechanical forces, which are exerted through focal adhesions, can activate myosin fibers could contribute to maturing the focal complexes.[6]

See also

References

  1. ^ Chen CS, Alonso JL, Ostuni E, Whitesides GM and Ingber DE, 2003. Cell shape provides global control of focal adhesion assembly. Biochemical and Biophysical Research Communications, 307(2):355–61.
  2. ^ Zaidel-Bar R, Cohen M, Addadi L and Geiger B, 2004. Hierarchical assembly of cell matrix adhesion complexes. Biochemical Society Transactions, 32(3):416-20.
  3. ^ Zamir E and Geiger B, 2001. Molecular complexity and dynamics of cell-matrix adhesions. Journal of Cell Science, 114(20):3583-90.
  4. ^ Riveline D, Zamir E, Balaban NQ, Schwarz US, Ishizaki T, Narumiya S, Kam Z, Geiger B and Bershadsky AD, 2001. Focal contacts as mechanosensors: externally applied local mechanical force induces growth of focal contacts by an mDia1-dependent and ROCK-independent mechanism. Journal of Cell Biology, 153(6):1175-86
  5. ^ Huttenlocher A, Palecek SP, Lu Q, Zhang W, Mellgren RL, Lauffenburger DA, Ginsberg MH and Horwitz AF, 1997. Regulation of cell migration by the calcium-dependent protease calpain. Journal of Biological Chemistry, 272(52):32719-22.
  6. ^ Wang Y, Botvinick EL, Zhao Y, Berns MW, Usami S, Tsien RY and Chien S., 2005. Visualizing the mechanical activation of Src. Nature, 434(7036):1040-5.
 
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