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REGULATION OF DESMOSOME FORMATION

 Regulation of desmosome assembly

The desmosome is an adherens like junction that is present in all epithelial tissues and is especially abundant in tissues that experience a lot of mechanical stress. Defects in desmosome formation or function can lead to cardiovascular disease, blistering and other skin disorders and tumor progression and metastasis. Therefore, understanding the assembly and biology of the desmosome is critical to our understanding of basic cellular processes and might provide important therapeutic leads for multiple diseases. Our work has demonstrated that two Armadillo (ARM) repeat containing proteins, Plakophilin3 (PKP3) and Plakoglobin (PG), play an important role in desmosome assembly. Loss of Plakophilin3 in multiple cell types results in a defect in the recruitment of other desmosomal components to the cell border resulting in a decrease in cell-cell adhesion (Figure 1). In contrast, PKP3 over-expression leads to an increase in cell-cell adhesion and an increase in the border localization of other desmosomal proteins. Similarly, our work has demonstrated that PG is required for the recruitment of PKP3 to the cell border and disrupting PG localization to the cell border leads to defects in desmosome function (Figure 1). The current work in the laboratory is focused on studying the mechanisms underlying desmosome formation in different cell types as it will help us understand this poorly understood but very important cell-cell junction.

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