THE CADHERIN SUPERFAMILY: BIOLOGICAL SIGNIFICANCE AND NEUROLOGICAL DIVERSITY
Zaharieva I*
*Corresponding Author: Dr. Irina Zaharieva, Department of Medical Genetics, Medical University Sofia, 2 Zdrave str, 1431 Sofia, Bulgaria; Tel./Fax: +359-2-952-03-57; E-mail: irinazaharieva@yahoo.co.uk
page: 19

DESMOSOMAL CADHERINS

The desmosomal cadherins are also single-pass trans­membrane proteins. Like the classical cadherins, they have five EC domains. They are known for their role in forming desmosomes, which, on their part, are sites of cell-cell adhesion found particularly in tissues subject to mech­anical strain (e.g., epidermis, myocardium). There are two subfamilies of desmosomal cadherins: the desmocollins (DSC) and the desmogleins (DSG) with distinct cytoplas­matic region, consisting of a cadherin-related region and catenin-binding C domain. The interaction with the cyto­plasmatic binding partners is through catenin-binding C domain. Each type in turn can be divided into three sub­types, depending on their expression in the different cells. Desmocollins and a DSG in combination mediate adhesion through their extracellular parts by homophilic or hetero­philic interactions between them and the apposed cells. Plakoglobin and DP are two of the cytoplastic partners. Plakcoglobin binds to the C domain of DSGs and DSCs through its armadillo repeats. Plakoglobin in turn interacts with DP which associates with the intermediate filaments. Plakoglobin can transduce signals to the nucleus by inter­acting with T-cell transcription factors (TCF). Plakophilins (PPs) are other members of armadillo family that can me­diate the link between desmosomal cadherins and the cyto­skeleton. This complex protein interaction involving des­mosomal cadherins, cytoplasmic partners and filament network leads to the formation of a structure, important to the stability of the respective tissues [3].

      Desmosomal cadherins are involved in signal trans­duction. Plakoglobin can transduce signals to the nucleus by interacting with TCF transcription factors, and through the Wnt pathway can regulate the expression of the anti-apoptotic protein BCL2 [10].




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