What are mature focal adhesions composed of?2018-02-05T16:52:05+00:00

What are mature focal adhesions composed of?

Mature FAs vary in size between 1 to 5 µm and to date, more than 80 types of proteins (~150 proteins) have been located in the FA plaque [1] although not all interactions have been proven in vivo. Several key components are shown to be organized into functional layers covering a distance of approximately 40 nm between the ECM-bound integrins and the actin cytoskeleton [2].

focal-adhesion-organization

A mature FA contains hundreds of proteins that are grouped based on their contribution to four basic processes: receptor/matrix binding, linkage to actin cytoskeleton, intracellular signal transduction, and actin polymerization. Both actin polymerization and actomyosin contractile machinery generate forces that affect mechanosensitive proteins in the actin linking module, the receptor module (e.g. integrins), the signaling module, and the actin polymerization module. The combined activity of the mechanosensitive components form the mechanoresponsive network. The theoretical organization and protein-protein interactions as shown are based upon references.

Amongst the FA components, the presence of zyxin and low levels of tensin distinguish mature focal adhesions from their earlier counterparts. These proteins are recruited through tyrosine phosphorylation events, with zyxin continually increasing in concentration during the tension-dependent maturation process ([3], reviewed in [4]). Zyxin also gets redistributed to stress fibers, thickens it and regulates adhesion reinforcement [5].

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References

  1. Zaidel-Bar R, Itzkovitz S, Ma'ayan A, Iyengar R, and Geiger B. Functional atlas of the integrin adhesome. Nat. Cell Biol. 2007; 9(8):858-67. [PMID: 17671451]
  2. Kanchanawong P, Shtengel G, Pasapera AM, Ramko EB, Davidson MW, Hess HF, and Waterman CM. Nanoscale architecture of integrin-based cell adhesions. Nature 2010; 468(7323):580-4. [PMID: 21107430]
  3. Beningo KA, Dembo M, Kaverina I, Small JV, and Wang YL. Nascent focal adhesions are responsible for the generation of strong propulsive forces in migrating fibroblasts. J. Cell Biol. 2001; 153(4):881-8. [PMID: 11352946]
  4. Zaidel-Bar R, Cohen M, Addadi L, and Geiger B. Hierarchical assembly of cell-matrix adhesion complexes. Biochem. Soc. Trans. 2004; 32(Pt3):416-20. [PMID: 15157150]
  5. Yoshigi M, Hoffman LM, Jensen CC, Yost HJ, and Beckerle MC. Mechanical force mobilizes zyxin from focal adhesions to actin filaments and regulates cytoskeletal reinforcement. J. Cell Biol. 2005; 171(2):209-15. [PMID: 16247023]