Cell membranes cadherins

Several nonconventional cadherins that contain cadherin repeats have been described but they have specific features not found in the classical cadherins [1]. The cadherin Flamingo, originally detected in Drosophila, contains seven transmembrane segments and in this respect resembles G protein-coupled receptors. The extracellular domain of Flamingo and its mammalian homologs is composed of cadherin repeats as well as EGF-like and laminin motifs. The seven transmembrane span cadherins have a role in homotypic cell interactions and in the establishment of cell polarity. The FAT-related cadherins are characterized by a large number of cadherin repeats (34 in FAT and 27 in dachsous). Their cytoplasmic domains can bind to catenins. T- (=truncated-)cadherin differs from other cadherins in that it has no transmembrane domain but is attached to the cell membrane via a glycosylpho-sphatidylinositol anchor. 

Adhesion molecules are indispensable components of nervous tissue. They adhere cell membranes to each other with varying degrees of strength and translate adhesion into cellular responses via signal-transduction pathways (see, for example, [45]). The major classes of adhesion molecules, the integrins, IgCAMs and cadherins, act cooperatively [46] and in concert to coordinate brain development and maturation and, in adulthood, to maintain the normal tissue architecture. 

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. 

Desmosomes are intercellular junctions, consisting of two cell membranes, separated by an interspace. The interspace contains dense fibrillar plaques rich in cell adhesion proteins of the cadherin type. Desmosomes are important for cell-cell adhesion and communication. Epithelial tissue in the body stretched mechanically is rich on desmosomes. 

The adhesion of cells to each other is normally due to interactions that involve a number of proteins of the extracellular matrix and the plasma membrane. Cadherin is a membrane-boimd protein. The N terminus of cadherin is extracellular. The N termini of cadherins sticking out of adjacent cells bind to each other. This interaction requires calcivun ions, hence the name Cadherin. An intracellular interaction is also required for adhesion to occur between cells. The C terminus of cadherin contacts the cytosol and binds to a protein called catenin (pronounced ca-TEE-nin). Catenin, in turn, binds to the cytoskeleton. The cytoskeleton is a network of proteins that crisscross about the plasma membrane and through the cell. Defects in the cadherin gene have been found in many samples of colorectal cancer. These mutations tend to occur in the N-terminal region, i.e., in the extracellular calcium-binding domain. 

Fig. 4. Structure of GPI-anchored T-cadherin. The extracellular domain contains four internal repeats EI-E4, an extra domain E5 and a lipid anchor for integration into cell membranes.

Immunoreactivity for calcitonin occurs in 27% of cases, whereas stains for gastrin-releasing peptide and serotonin have been reported in 39% and 14%, of cases, respectively. Estrogen and progesterone receptor positivity have been reported in 54%, and 45%, respectively. Bcl-2 is consistently positive, but stains for HER-2/neu are negative.CD 99 has been reported in 3 of 3 cases of small cell carcinomas and cell membrane immunoreactivity for E-cadherin in 11 of 12 (92%) of reported cases... 

The active toxin has two main functional entities, responsible for receptor binding and ion channel activity, respectively. The activated toxin binds to receptors, which seem to be of different types, on the midgut microvilli of the susceptible insects. Different toxins seem to bind to different receptor proteins that may be an enzyme such as aminopeptidase or alkaline phosphatase, or a cadherin-like membrane protein. (The cadherins are proteins that are important in keeping the cells together by mediating Ca+-dependent cell-cell adhesion in animal tissue.) The toxins are anchored to the outer epithelial cell membrane in such a way that the membrane is perforated by pores or channels where ions can freely pass. This model proposes that an influx of water, along with ions, results in swelling and lysis. The epithelium is destroyed and the insect rots. 

Adhesion protein E-cadherin Cell membrane Stomach cancer... 

Hynes RO (2004) The emergence of integrins a personal and historical perspective. Matrix Biol 23 333-340 Ino Y, Gotoh M, Sakamoto M et al (2002) Dysadherin, a cancer-associated cell membrane glycoprotein, down-regu-lates E-cadherin and promotes metastasis. Proc Natl Acad Sci USA 99 365-370... 

Although cadherins do not exclusively cluster, the formation of adherens junctions is important for several tissue functions [18]. In epithelial tissues cadherins mediate zonula adherens junctions, which partition the cell membrane into apical and basolateral surfaces. In neuronal cells they mechanically stabilize synaptic junctions by mediating adhesion between the presynaptic and postsynaptic cells. In cardiac myocytes they establish intercalated discs, which both stabilize gap junctional coupling and transmit contractile forces. 

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. 

PSl forms a complex with p-catenin (CTNNBl), increasing P-catenin stability, and P-catenin levels are markedly reduced in the brains of AD patients with PSl mutations (157). One pathological characteristic of AD is extensive synapse loss. PSl is localized at the synapse, where it binds N-cadherin and modulates its adhesive activity. PSl is essential for efficient trafficking of N-cadherin from the ER to the plasma membrane. PW-mediated delivery of N-cadherin to the plasma membrane is important for N-cadherin to exert its physiological function, and it may control the state of cell-cell contact (158). 

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