Cell adhesion molecules cadherins

Cadherins are a superfamily of Ca2+-sensitive cell-cell adhesion molecules, which cause homophilic cell interactions. Cadherins can be divided into different subfamilies, namely, classical cadherins, desmosomal cadherins, protocadherins, and nonconventional cadherins (7TM cadherins, T-cadherin, FAT). Classical cadherins are often denoted by a prefix reflecting their principal expression domains e.g., E is epithelial, N is neuronal, and P is placental. However, this classification is not stringent, as for instance E-cadherin can also be found in certain neuronal tissues, and N-cadherin is also found in epithelial cells. Among the desmosomal cadherins, two subfamilies can be distinguished the desmocollins 1-3 and the desmogleins 1-4. 

The extracellular domain of cadherins consists of a variable number of a repeated sequence of about 110 amino acids. This sequence is termed the cadherin repeat and resembles in overall structure, but not in sequence, the Ig like domains. The cadherin repeat is the characteristic motive common to all members of the cadherin superfamily. Classical and desmosomal cadherins contain five cadherin repeats, but as many as 34 repeats have been found in the FAT cadherin (see below). Cadherins are calcium-dependent cell adhesion molecules, which means that removal of Ca2+, e.g., by chelating agents such as EDTA, leads to loss of cadherin function. The Ca2+-binding pockets are made up of amino acids from two consecutive cadherin repeats, which form a characteristic tertiary structure to coordinate a single Ca2+ion [1]. 

Integrins, selectins, cadherins, claudins and other cell adhesion molecules are involved in the interaction of cells with other cells or with extracellular matrix components. Some of them also serve as receptors by inducing outside-in or additional inside-out signaling. 

WJ Nelson, EM Shore, AZ Wang, RW Hammerton. (1990). Identification of a membrane-cytoskeletal complex containing the cell adhesion molecule uvomorulin (E-cadherin), ankyrin, and fodrin in Madin-Darby canine kidney epithehal cells. J Cell Biol 110 349-357. 

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. 

Recent experiments have suggested that the tip link, a complex of two or three braided glycoprotein filaments [19], may be made in part from cadherin-23, a Ca2+-dependent cell-adhesion molecule [20], Moreover, cadherin-23 can interact directly or indirectly with myosin- lc, suggesting that these two molecules form part of the transduction complex in hair cells [20]. 

The cell surface additionally displays receptors responsible for cell-cell recognition [28]. Members of this class of receptors are selectins [29] that recognize specific carbohydrates from other cells in the presence of calcium. Other cell surface receptors belong to the immunoglobulin superfamily (IgSF) [30] that promote calcium-independent cell-cell adhesion. The third important class are the calcium-dependent cell adhesion molecules, the cadherins [31], which form dimers with cadherin molecules presented on the surfaces of other cells and hence promote aggregation of similar cell types. 

Cadherins are calcium-dependent cell-cell adhesion molecules. Most cadherins are transmembrane glycoproteins consisting of five repeated extracellular... 

Initially characterized as an autoantigen in a human connective tissue disease [62]. May be associated with methylation induced gene silencing and heterochromatin [64,65,103]. Interacts with a component of DNA repair machinery [308]. Functions in estrogen dependent repression of Snail. Aberrant Snail expression results in loss of expression of the cell adhesion molecule E-cadherin, an event associated with invasive growth of breast cancers [309]. 

Aplin, A.E., Howe, A., Alahari, S.K., Jiiliano, R.L. (1998) Signal transduction and signal modulation by cell adhesion receptors the role of integrins, cadherins, immunoglobulin-cell adhesion molecules, and selectins. Pharmacol. Rev. 50, 197-263. 

The contacts between two adjoining cell membranes are stabilized by specific cell adhesion molecules (CAMs), which include the Ca+2-dependent cadherins. These molecules appear to lead the way for cell-cell communications and are involved in mechanochemical transduction via cell-cell interactions. In some cell types, cadherins are concentrated within adherens junctions that are stretch-sensitive and their extracellular domains interact with cadherins on adjacent cells whereas their cytoplasmic domains provide attachment to the actin cytoskeleton via catenins and other cytoskeletal proteins. The Rho family is required for the establishment and maintenance of cadherin-based adherens junctions. The type of cadherin expressed in a cell can affect the specificity and the physiological properties of cell-cell interactions. 

VE)-cadherin and platelet endothelial cell adhesion molecule-1 (PECAM-1). VE-cadherin is an endothelial-specific Ca " -regulated protein that is linked to the cytoskeleton via catenins (Fig. 1). PECAM-1, also known as CD31, is a key participant in the migration of blood-borne cells across the BBB. Changes in the adherent junction proteins can lead to increased paracellular permeability (Abbruscato and Davis, 1999) and leukocyte trafficking in the CNS (Newman, 1994 Garrido-Urbani et al., 2008). 

Epithelial cadherin (E-cadherin) has a molecular weight of 130 kDa and is found in PNS myelin. E-cadherin is a protein of the superfamily of calcium-dependent cell adhesion molecules that can usually form adherent junctions. This protein has an N-terminal extracellular domain, a short transmembrane domain and a C-terminal intracellular domain. 

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