Integrin adhesion receptors structure

The integrins (see also p. 405) comprise a large family of adhesive receptors that are found in animals from sponges to humans. " They have both adhesive and signaling functions. Both subunits of their heterodimeric structures have single transmembrane... 

Another feature of tumor cells, particularly those with high malignancy, is the loss of cellular polarity. Normal, non-transformed cells, with the exception of blood cells, have a clearly polarized structure i) surface membrane structure involved in cell-to-cell or cell-to-extracellular matrix adhesion ii) surface structure open to the external environment and involved in endocytosis or exocytosis. Structure (i) in epithelial cells, termed basolateral surface, is rich in adhesion receptors including integrins (ii), termed apical surface, has much higher level of sphingolipids,... 

Figure 48-3. Schematic representation of fibronectin. Seven functional domains of fibronectin are represented two different types of domain for heparin, cell-binding, and fibrin are shown. The domains are composed of various combinations of three structural motifs (I, II, and III), not depicted in the figure. Also not shown is the fact that fibronectin is a dimer joined by disulfide bridges near the carboxyl terminals of the monomers. The approximate location of the RGD sequence of fibronectin, which interacts with a variety of fibronectin integrin receptors on cell surfaces, is indicated by the arrow. (Redrawn after Yamada KM Adhesive recognition sequences.

The domain structure in fibronectins is made up of a few types of peptide module that are repeated numerous times. Each of the more than 50 modules is coded for by one exon in the fibronectin gene. Alternative splicing (see p. 246) of the hnRNA transcript of the fibronectin gene leads to fibronectins with different compositions. The module that causes adhesion to cells contains the characteristic amino acid sequence -Arg-Gly-Asp-Ser-. It is these residues that enable fibronectin to bind to cell-surface receptors, known as integrins. 

Integrins are widely expressed cell surface receptors involved in cell-cell adhesion and interactions of cells with the extracellular matrix. Integrins enable the cellular uptake of structures as large as bacteria and as small as viruses. Thus, they constitute good targets for developing selective gene delivery systems. 

E-cadherin is unique in that it not only, like other cadherin family members, mediates homophilic adhesion to establish and maintain cellcell contacts, it also serves as a counter-receptor for integrins Oe/37 (Cepek et al, 1994) and (Whittard et al, 2002) in heterophilic adhesion. In fact, the interaction between E-cadherin on mucosal epithelial cells and Oe/S on intraepithelial lymphocytes has been the best characterized tissue-specific interaction for lymphocyte retention. Although structure of binding domains between E-cadherin and is not available, mutagenesis... 

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