p0071/PKP4, a multifunctional protein coordinating cell adhesion with cytoskeletal organization

Abstract

P0071 is a member of a subfamily of armadillo proteins that also comprises p120-catenin (p120ctn), δ-catenin/NPRAP, ARVCF and the more distantly related plakophilins 1-3. These proteins share a conserved central domain consisting of a series of repeated motifs, the armadillo repeats, which is flanked by more diverse amino- and carboxy-terminal domains. P0071 and the related proteins were first described as components of adherens junctions with a function in clustering and stabilizing cadherins, thereby controlling intercellular adhesion. In addition, these proteins show a cytoplasmic and a nuclear localization. Major progress in understanding their cytoplasmic role has been made in recent years. One common theme appears to be the spatiotemporal control of the small GTPases of the Rho family in various cellular contexts, such as cell adhesion and motility, cell division or neurite outgrowth. In this review article, we focus on the functions of the p0071 protein and its closest relatives in regulating cell adhesion and cytoskeletal organization, which are critically involved in the control of cell polarity. Understanding p0071's multiple functions requires assigning specific functions to particular binding partners and subcellular compartments. The identification of several new p0071 interacting proteins has promoted our understanding of the complex functions of this protein. Moreover, an initial analysis of its regulation begins to shed light on how these functions are coordinated in a cellular context.