Desmosomes

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]. 

Classical and desmosomal cadherins are constituents of different types of intercellular junctions. E-cadherin, the classical cadherin of epithelial cells, is part of the adherens junction (zonula adherens), which is attached to a belt of actin via the catenins. As the name says, desmosomal cadherins are part of the desmosomes, which are rivet-like structures that make focal connections between cells. Desmosomes are characterized by a... 

Desmoplakin is the most abundant desmosomal component that plays a critical role in linking intermediate filament networks to the desmosomal plaque. Desmoplakin forms rod-like dimers that bind to intermediate filaments and to the cadherin-associated proteins plakoglobin and plakophilin. Gene knock-out experiments have revealed an essential role of desmoplakin in establishing cell-cell contacts in early mouse embryos. 

Inside the typical smooth muscle cell, the cytoplasmic filaments course around the nuclei filling most of the cytoplasm between the nuclei and the plasma membrane. There are two filamentous systems in the smooth muscle cell which run lengthwise through the cell. The first is the more intensively studied actin-myosin sliding filament system. This is the system to which a consensus of investigators attribute most of the active mechanical properties of smooth muscle. It will be discussed in detail below. The second system is the intermediate filament system which to an unknown degree runs in parallel to the actin-myosin system and whose functional role has not yet been completely agreed upon. The intermediate filaments are so named because their diameters are intermediate between those of myosin and actin. These very stable filaments are functionally associated with various protein cytoarchitectural structures, microtubular systems, and desmosomes. Various proteins may participate in the formation of intermediate filaments, e.g., vimentin. 

Figure 6 An electron micrograph of intercellular junctions between two human colon Caco-2 cells in culture. D, desmosome LS, lateral space mv, microvilli ZA, zonula adherens ZO, zonula occludens (i.e., tight junction). Bar equals 200 nm.

Skeletal and cardiac muscles also have important differences. Skeletal muscle cells are elongated and run the length of the entire muscle furthermore, these cells have no electrical communication between them. Cardiac muscle cells, on the other hand, branch and interconnect with each other. Intercellular junctions found where adjoining cells meet end-to-end are referred to as intercalated discs. Two types of cell-to-cell junctions exist within these discs. Desmosomes hold the muscle cells together and provide the structural support needed when the heart beats and exerts a mechanical... 

FIGURE 1-11 An electro tonic synapse is seen at the surface of a motor neuron from the spinal cord of a toadfish. Between the neuronal soma (left) and the axonal termination (right), a gap junction flanked by desmosomes (arrows) is visible. (Photograph courtesy of Drs G. D. Pappas and J. S. Keeter.) X80,000. 

FIGURE 1-18 A typical desmosome (d) and gap junction (g) between two ependymal cells. Microvilli and coated pits (arrows) are seen along the cell surface. X35,000. 

The biochemical properties of these structures are known. Desmosomes display protease sensitivity, divalent cation dependency and osmotic insensitivity and their membranes are mainly of the smooth type. In direct contrast to desmosomes, the tight junctions as well as gap junctions and synapses display no protease sensitivity, divalent cation dependency or osmotic sensitivity, while their membranes are complex. These facts have been used in the development of techniques to isolate purified preparations of junctional complexes. 

A recent crystal structure based model [20] for the structure of C-cadherin postulates that the five extracellular domains EC1-EC5 protrude from the cell surface as a curved rod. The structural analysis of C-cadherin reveals that the molecules facing each other across apposed cell surfaces are antiparallel to one another, forming a dimeric interaction termed a strand dimer (Fig. 7-5). This forms the functional unit that is likely to mediate adhesion between cell surfaces. The structure from this recent paper allows the prediction of both cis and trans interfaces that together result in a lattice and not, as previously believed, an adhesion zipper. This new model allows for a mechanism by which adhesion plates or puncta might be generated, such as are formed at CNS synapses [21, 22], adherens junctions and desmosomes [23], all cadherin based organelles. 

He, W., Cowin, P. and Stokes, D. L. Untangling desmosomal knots with electron tomography. Science 302 109-113, 2003. 

The columnar, cuboidal basal cells are 18-20 xm in height and 8-10 iim in diameter. They form a monolayer adhered to a basement membrane by hemidesmosomes which are linked to anchoring fibrils of collagen type VII. At the lateral borders, basal cells are extensively interdigitated and joined together in places only by junctional complexes (zonula adherens), desmosomes, and gap junctions. 

The first immortalized cell line to gain major impact in the development of corneal epithelial cell clones was the rabbit corneal epithelial cell line (RCE, also known as K RCE) introduced by Araki et al. in 1993 [51], Corneal epithelial cells from a New Zealand albino rabbit were transfected with an SV40-vector. After transfection, the cells grew with cobblestone-like appearance and showed stratification, desmosomes, microvilli, and some typical types of... 

It has been shown that IFN-y induces Fas on keratinocytes which renders them susceptible to apoptosis induction by infiltrating FasL+ T cells. This has been interpreted as an important event in eczema, mainly in atopic dermatitis. There is further evidence that cleavage of E-cadherin and sustained desmosomal cadherin contacts between keratinocytes that are undergoing apoptosis result in spon-gioform morphology in the epidermis as a hallmark of eczematous lesions. Suppression of keratinocyte activation and apoptosis thus remains a potential target for the treatment of atopic dermatitis [2]. 

Fig. 9. Distribution of the gap junctions, desmosomes and fascia adherens in an intercalated disk of a cardiomyocyte as assessed by electron microscopy of freeze-fractured rat and rabbit hearts according to Severs [1990]. 

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