Funktion von Plakophilin 1 bei der Regulation von Zelladhäsion und Zellwanderung

一些研究结果表明，plakophilin 1可能参与调节粘附和运动之间的平衡：（1）plakophilin 1的缺失突变体诱导丝状伪足的形成和（2）由plakophilin 1的缺失引起的遗传性皮肤病导致表皮角质形成细胞粘附减少。在最后一个时期的补助金，我们已经表明，高表达水平的plakophilin 1诱导招聘内源性桥粒蛋白质膜，从而促进连接形成。氨基末端结构域对于该功能是必要且充分的。该结构域直接与两种桥粒蛋白，桥粒芯糖蛋白1和桥粒斑蛋白相互作用。相反，过表达的犰狳重复区干扰单层形成，并导致细胞间粘附的损失。Plakophilin 1与丝状伪足中的肌动蛋白丝共定位。我们发现，一个保守的序列基序在中心的犰狳重复区是必不可少的肌动蛋白协会表明plakophilin 1相关蛋白具有类似的功能，在调节肌动蛋白细胞骨架。我们计划更详细地分析肌动蛋白和plakophilin 1臂重复序列之间的相互作用，并阐明plakophilin 1在信号转导中的功能及其在调节粘附中的作用。

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.