- Focal adhesion
In
cell biology , focal adhesions (also cell-matrix adhesions or FAs) are specific types of largemacromolecular assemblies through which both mechanical force and regulatory signals are transmitted. More precisely, they can be considered as sub-cellularmacromolecules that mediate the regulatory effects (e.g. cell anchorage) ofextracellular matrix (ECM) adhesion on cell behavior. [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.]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.tructure and function
Focal adhesions are large, dynamic
protein complexes through which thecytoskeleton of a cell connects to theextracellular 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. [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.] 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 fromcell motility tocell cycle . Focal adhesions can contain over 100 different proteins, which suggests a considerable functional diversity. [Zamir E and Geiger B, 2001. Molecular complexity and dynamics of cell-matrix adhesions. "Journal of Cell Science", 114(20):3583-90.] 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. [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] In 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 theimmune system , in whichwhite blood cells migrate along the connectiveendothelium following cellular signals and to damagedbiological tissue .Morphology
Connection between focal adhesions and proteins of the
extracellular matrix generally involves the proteinintegrin . Integrin binds to extra-cellular proteins via short amino acid sequences, such as the R-G-Dsequence motif (found in proteins such asfibronectin ,laminin , orvitronectin ), or the DGEA and GFOGER motifs found incollagen . Integrins areheterodimers which are formed from one beta and one alpha subunit. These subunits are present in different forms, which differ in their specificity and affinity to the different ECM proteins. Within the cell, the intracellular domain of integrin binds to the cytoskeleton via adapter proteins such as talin, α-actinin,filamin andvinculin . Many other intracellular signalling proteins, such asfocal 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 inlamellipodia : they consist of integrin, and some of the adapter proteins, such as talin andpaxilin . Many of these focal complexes fail to mature and are disassembled as the lamellipodia withdraws. However, some focal complexes mature into larger and stable focal adhesions, and recruit many more proteins such aszyxin . Once in place, a focal adhesion remains stationary with respect to the extracellular matrix, and the cell uses this as an anchor on which it can push or pull itself over the ECM. As the cell progresses along its chosen path, a given focal adhesion moves closer and closer to the trailing edge of the cell. At the trailing edge of the cell the focal adhesion must be dissolved. The mechanism of this is poorly understood and is probably instigated by a variety of different methods depending of the circumstances of the cell. One possibility is that the calcium-dependent proteasecalpain 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 [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.]Natural biomechanical sensor
Extracellular mechanical forces, which are exerted through focal adhesions, can activate
Src kinase and stimulate the growth of the adhesions. This indicates that focal adhesions may function as mechanical sensors, and suggests that force generated frommyosin fibers could contribute to maturing the focal complexes. [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.]ee also
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Actin
*TES (protein) References
External links
* [http://www.unifr.ch/histologie/elearningfree/allemand/epithel/epithel05.html Intercellular Connections]
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