Funktion von Plakophilin 1 bei der Regulation von Zelladhäsion und Zellwanderung

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Several findings suggested that plakophilin 1 might be involved in regulating the balance between adhesion and motility: (1) A deletion mutant of plakophilin 1 induced the formation of filopodia and (2) a genetic skin disease caused by the loss of plakophilin 1 results in reduced adhesion of epidermal keratinocytes. During the last period of the grant we have shown that high expression levels of plakophilin 1 induce recruitment of endogenous desmosomal proteins to the plasma membrane thereby facilitating junction formation. The amino-terminal domain is necessary and sufficient for this function. This domain interacts directly with two desmosomal proteins, desmoglein 1 and desmoplakin. In contrast, overexpression of the armadillo repeat region interferes with monolayer formation and results in a loss of intercellular adhesion. Plakophilin 1 colocalizes with actin filaments in filopodia. We show that a conserved sequence motif in the center of the armadillo repeat region is essentiell for actin association suggesting that plakophilin 1 related proteins have a similar function in regulating the actin cytoskeleton. We plan to analyze the interaction between actin and the plakophilin 1 arm repeats in more detail and to elucidate for function of plakophilin 1 in signal transduction and its role in regulating adhesion.