Adhesion complex

FAT Focal adhesion targeting domain Binding to focal adhesions complexes... 

Integrins present in focal adhesion complexes cause the recruitment of two types of protein tyrosine kinases to the plasma membrane focal adhesion kinase (FAK) and Src. They play a role in cell survival and proliferation. 

Borradori, L., and Sonnenberg, A. (1999). Structure and function of hemidesmosomes More than simple adhesion complexes. / Invest. Derm. 112, 411—118. 

Yamada, K.M., and B. Geiger. 1997. Molecular interactions in cell adhesion complexes. Curr Opin Cell Biol. 9 76-85. 

Desmoplakins I and n are key plaque proteins which anchor desmosomes to keratin filaments in the epidermis. Desmosomes are critical adhesion complexes between adjacent epithelial cells, that assemble in response to cell-cell contact and raised levels of extracellular Ca2+ (Green and Gaudry, 2000). SERCA2 and desmoplakins have been shown to interact in a Ca2+ dependent manner on the ER membrane in cultured human primary keratinocytes, suggesting that SERCA2 may have an accessory function in desmosomal assembly (Dhitavat et al., 2003a). 

Despite this complexity, most integrins share two, key interrelated functions first, to promote the assembly and organization of the actin cytoskeleton [122, 123] and second, to regulate signal transduction cascades [124-126], Spanning the cell membrane, these subunits serve as a communication pathway, linking the actin cytoskeleton and intracellular cytoplasmic proteins involved in focal adhesion complexes (FACs) with the cell s dynamic extracellular environment (Fig. 8) [127-130]. There are at least 50 distinct proteins known to be involved in FACs. Actin [131], vinculin, talin, tensin, a-actinin, and filamin provide a structural role, while focal adhesion kinase [132], integrin-linked kinase, Src-family kinase, PINCH, paxillin... 

ECM, cytoplasmic proteins, and the actin cytoskeleton in formation of a focal adhesion complex... 

The structural integrity of microfilaments has been shown to be necessary for signal transduction within osteoblasts. Examination of the effects of mechanical strain on the expression of major structural elements of the cytoskeleton indicated that the amount of tubulin decreased by 75% and the amount of vinculin, a major component of focal adhesion complexes, increased by about 250%. Immunofluorescence microscopy demonstrated that mechanical strain led to increased formation and thickening of actin stress fibers, with dissociation of the microtubules and a clear increase in levels of vinculin at the peripheral edges of the cell. This suggests that mechanical strain leads to a coordinated change in both the cytoskeleton and in ECM proteins that facilitate tighter adhesion of osteoblasts and their ECM. 

The explosion of science in the latter half of the 20th century, elueidating eomponents of the adhesion complex between the epithelial and stromal layers of the cornea, suggest the basement membrane zone may become a target area for therapy in the future. Indeed, protease inhibitors of enzymes that remodel the basement membrane show promise as eountermeasures. Using rabbits for an ocular SM vapor challenge, the matrix metalloprotease inhibitors... 

Werrlein, R.J., Madren-Whalley, J.S. (2000). Effects of sulfur mustard on the basal cell adhesion complex. J. Appl. Toxicol. 20 S115-23. 

A specialized cell-matrix contact point, which is stracturaUy distinct from focal adhesion complexes. See Linder, S. and Aepfelbacher, M., Podo-somes adhesion hot-spots of invasive cells. Trends Cell Biol. 13, 376-385, 2003 McNiver, M.A., Baldassarre, M., and Buccione, R., The role of dynamin in the assembly and function of podosomes and invadopodia. Front. Biosci. 9, 1944-1953, 2004 Linder, S., and Kopp, R, Podosomes at a glance, J. Cell Sci. 118, 2079-2082, 2005. 

RCEs are reoccurring episodes of spontaneous breakdown or sloughing of the epithelial layer of the cornea. RCEs are caused by poor adhesion complexes between the epithelial basement membrane and Bowman s layer. 

A tempting model has been proposed that, upon recruitment to focal adhesion complexes, FAK undergoes conformational change and interacts through its amino terminal domain with the integrin cytoplasmic tail (43-45). The amino terminal domain of... 

Hotchin NA, HaU A. The assembly of integrin adhesion complexes requires both extraceUular matrix and intracellular rho/rac GTPases. J. Cell. Biol. 1995 131 1857-1865. 

Butler B, Gao C, Mersich AT, Blystone SD. Purified integrin adhesion complexes exhibit actin-polymerization activity. Curr. 

H. Shroff et ah. Dual-color superresolution imaging of genetically expressed probes within individual adhesion complexes. Proc. Natl. Acad. Sci. U.S.A. 104(51), 20308-20313 (2007)... 

Toxicants that reduce ATP disrupt cell volume, ion concentrations, and cell polarity. Disruption of cell volume and ion homeostasis occurs by toxicant interaction with the plasma membrane increasing ion permeability or by attenuahng energy produchon. ATP depletion results in a decrease in Na, K -ATPase activity, resulting in cell swelling, and ultimately cell rupture [54, 55]. The tubular epithelia are polarized cells with specific transporters on the apical and basolateral domains. When a toxicant causes ATP depletion there is a dissociation of the Na, K -ATPase from the actin cytoskeleton and a redistribution from the basolateral to apical domain in the renal proximal tubule cells [56]. The loss of polarity of the cells disrupts the adhesion complexes and loss of cell-to-cell contact that facilitates further renal damage. 

Several years ago, while visiting a plastics and adhesive complex in the Far East, a worker confided in me that male colleagues of his working with acrylics were less fecund than those in the complex who did not work with acrylics and that when they did succeed in impregnating their wives, 80% of the children born were female. Acrylic polymers are not known to be antiandrogenic, but some of their plasticizers (such as bisphenol A and... 

Stutzmann J, Bellissent-Waydelich A, Fontao L, Launay JF, Simon-Assmann P. Adhesion complexes implicated in intestinal epithelial cell-matrix interactions. Microsc Res Tech 2000,15 Oct 51(2) 179-190. 

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