T-Cadherin

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. 

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.

Recently, several novel members of the cadherin family have been discovered M-cadherin in mouse embryonic skeletal muscle [35,36], R-cadherin in neuronal cells [37] and T-cadherin in myoblasts [38]. The structure of T-cadherin (Fig. 4) is of special interest. This cadherin in its mature form lacks the transmembrane and cytoplasmic domains of classical cadherins and is integrated into the membrane by a GPl anchor. Although T-cadherin is a severely truncated form and additionally lacks an HAV sequence in the El domain it appears to be functional. Transfection of cDNA encoding T-cadherin into a cell devoid of cadherin expression confers calcium-dependent aggregation on the cells [38]. The mechanism of T-cadherin adhesion is intriguing and presumably is independent of interactions with catenins and direct coupling with actin filaments. 

T-cadherin (truncated) K-CAM (near identity with B-cadherin) Early embryo... 

Ranscht, B. Bronner-Fraser, M. (1991). T-cadherin expression alternates with migrating neural crest cells in the trunk of... 

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. 

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Hipp S, Walch A, Schuster T, et al. Precise measurement of the E-cadherin repressor Snail in formalin-fixed endometrial carcinoma using protein lysate microarrays. Clin. Exp. Metastasis 2008 25 679-683. 

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Fulimoto J, Sakaguchi H, Hirose R, Tamaya T (1998) Sex steroidal regulation of vessel permeability associated with vessel endothelial cadherin (v-cadherin). J Steroid Biochem Mol Biol 67 25-32... 

Evans SM, Blyth DI, Wong T, Sanjar S, West MR (2002) Decreased distribution of lung epithelial junction proteins after intratracheal antigen or lipopolysaccharide challenge correlation with neutrophil influx and levels of BALF sE-cadherin. Am J Respir Cell Mol Biol 27(4) 446-454... 

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]. 

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L. J., Heckel, D.G., Carriere, Y., Dennehy, T.J., Brown, J.K., and Tabashnik, B.E., Three cadherin alleles associated with resistance to Bacillus thuringiensis in pink bollworm, Proc. Natl. Acad. Sci. USA, 100, 5004, 2003. 

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