Cadherin-like proteins

In H. virescens, loss of expression of a cadherin-like protein was found to be associated with CiylA toxin resistance and consequently this protein plays a crucial role in B. thuringiensis toxicity in vivo [149]. In the laboratory-selected resistant H. virescens strain YHD2, a retrotransposon insertion in the cadherin gene was linked to high levels of CtylAc resistance. More recently, disruption of a cadherin gene may also be linked to the development of field resistance to CiylA toxins in the pink boUworm, Pectinophora gossypiella [150]. 

Figure 4. M. sexta cadherin-like protein showing predicted sequence motifs...

The cadherin-like proteins have been successfully expressed in heterologous systems and the recombinant proteins have similar toxin-binding capabilities as the native proteins [133,151-153]. Insect cells expressing the cadherin-like protein also exhibited CrylAa toxin-induced cell swelling and whole cell patch clamp measurements indicating possible pore formation [147]. 

The significance of cadherin-like proteins as receptors has been demonstrated by ectopic expression in different cell lines [12, 13] and is further corroborated by the presence of mutated cadherin genes in resistant Hdiothis virescens [14, 15] and Pectinophora gossypidla [16, 17] insect strains. In addition, glycolipids and glycosylated alkaline phosphatase have been implicated in Cry binding [18, 19]. 

Nagamatsu, Y., T. Koike, K. Sasaki, A. Yoshimoto, and Y. Furukawa. 1999. The cadherin-like protein is essential to specificity determination and cytotoxic action of the Bacillus thuringiensis insecticidal CrylAa toxin. FEES Lett. 460 385-390. 

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. 

Fujita Y, Krause G, Scheffner M et al (2002) Hakai, a c-Cbl-like protein, ubiquitinates and induces endo-cytosis of the E-cadherin complex. Nat Cell Biol 4(3) 222-231... 

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. 

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. 

A typical example of a proto-oncogene translocation is the membrane tyrosine kinase receptor RET [see review (Santoro et al. 2004)]. The outer membrane part consists of four cadherin-like domains the inner membrane domain has the tyrosine kinase activity. The gene was discovered in 1985 and was found to be activated by a DNA rearrangement, a mechanism giving the gene its name (Rearranged during Transfection). RET protein has several tyrosine residues that are auto-phosphory-lated. The phosphorylation of the tyrosine 905 is sug-... 

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. 

The cadherins are calcium-dependent adhesion proteins that mediate direct cell-cell interactions.295 296 The external parts of the cadherins also have repeated structural domains with the Ig fold.297 298b They have high affinity for each other, allowing cadherins from two different cells to interact and tie the cells together with a zipper-like interaction that is stabilized by the bound Ca2+ ions,297 300 and may be relatively long-lived. The gene for cadherin E is often mutated in breast cancers and may be an important tumor suppressor gene (Box 11-D).301... 

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