Cadherins homophilic binding

The classic cadherins are homophilic adhesion molecules. That is, E-cadherin expressed on one cell surface binds to E-cadherin expressed on an apposed cell surface, N-cadherin binds to N, P to P and so forth. It was originally thought that all cadherins would behave completely homophilically but it is now clear that, for example, N-cadherin can bind to R-cadherin, although perhaps more weakly than it would to N-cadherin. 

Although E-cadherins exhibit primarily homophilic binding, some cadherins mediate heterophilic interactions. Importantly, each classical cadherin has a characteristic tissue distribution. In the course of differentiation, the amount or nature of the cell-surface cadherins changes, affecting many... 

Cadherins Transmembrane glycoprotein, I20-I40 kDa Plasmalemma Ca -dependent homophilic binding to extracellular domain, cytoskeletal binding to cytosol domain Maintenance of cell-cell interactions... 

Within each of these adhesion molecule families, membership has been defined largely by amino-acid sequence similarity, which is reflected in common structural features. Consequently, distinct binding requirements also characterize each family. For example, cadherins interact in a Ca2+-dependent, usually homophilic manner. Binding of the members of the Ig family is Ca2+-independent and, although frequently homophilic, can be heterophilic. Integrin binding is also divalent cation-dependent (Ca2+, Mg2+) but always heterophilic. 

Adhesion molecules such as LI, neural cell adhesion molecule (N-CAM) and N-cadherin promote axonal regeneration by homophilic interactions between axons and Schwann cell surfaces (see Ch. 7). The expression of p75 (low affinity NGF receptor, Ch. 27) is also increased at the Schwann cell surface after injury. Extracellular matrix molecules, such as tenascin and proteoglycans, increase the regenerative potential of damaged peripheral nerves by binding to integrins on the axonal surface. 

At least three other families of plasma membrane proteins are also involved in surface adhesion (Fig. 11-22). Cadherins undergo homophilic ( with same kind ) interactions with identical cadherins in an adjacent cell. Immunoglobulin-like proteins can undergo either homophilic interactions with their identical counterparts on another cell or heterophilic interactions with an integrin on a neighboring cell. Selectins have extracellular domains that, in the presence of Ca2+, bind specific polysaccharides on the surface of an adjacent cell. Selectins are present primarily in the various types of blood cells and in the endothelial cells that line blood vessels (see Fig. 7-33). They are an essential part of the blood-clotting process. 

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... 

Cadherins are Ca -binding adhesion molecules that mediate homophilic interaction between cells. Cadherins are particularly important for selective fasciculation of regenerating axons. For instance, E-cadherin mediates attachment of unmyelinated sensory fibers and stabilizes glial network [42], and N-cadherin mediates axon-Schwann ceU interactions during regeneration [39, 43]. 

A FIGURE 6-7 Protein constitutents of typical adherens junctions. The exoplasmic domains of E-cadherin dimers clustered at adherens junctions on adjacent cells (1 and 2) form Ca -dependent homophilic interactions. The cytosolic domains of the E-cadherins bind directly or indirectly to multiple adapter proteins that connect thejunctions to actin filaments (F-actin) of... 

In this experimental system, the addition of an antibody that binds to E-cadherin, preventing Its homophilic Interactions, blocks the Ca " -dependent attachment of suspended MDCK cells to a substrate and the subsequent formation of intercellular adherens junctions. 

Cadherins are the main receptors for calcium-dependent cell-cell adhesion in most solid tissues (Alberts et al. 2002). Besides being responsible for the mechanical stability, they coordinate the integration of cells in functional structures like the epithelium and control cell movement in tissue development and organization, especially during embryogenesis (Table 5.3). Classical cadherins are transmembrane glycoproteins, which bind almost exclusively to the same type of receptor expressed on the other cell in a homophilic manner (Fig. 5.2). The intracellular domain is connected to the cytoskeleton via a group of anchor proteins known as catenins (Pettitt 2005 Reynolds 2007). This link-... 

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