Plakophilin-3, a novel Armadillo-like protein

Armadillo-like (Arm) proteins are characterized by a series of repeats of 42-45 amino acid residues (aa), originally described in the Drosophila protein Armadillo (Riggleman et al., 1989). These Arm repeats have meanwhile been detected in a wide variety of proteins in a number of organisms, even including plants (Lo and Frasch, 1998; Peifer et al., 1994; Vithalani et al., 1998; Wang et al., 1998). β-catenin is probably the most extensively studied Arm protein at the moment. The protein acts as a mediator of cell-cell adhesion through the Ecadherin/catenin complex in epithelial cells (Aberle et al., 1994; Ozawa et al., 1989). However, β-catenin is also a regulator of gene transcription via its interaction with LEF1/TCF transcription factors (Behrens et al., 1996; Molenaar et al., 1996). In the E-cadherin/catenin cell adhesion complex, either β-catenin or γ-catenin (also known as plakoglobin) links the cytoplasmic domain of E-cadherin to the actin cytoskeleton via αE-catenin (Herrenknecht et al., 1991; Knudsen et al., 1995; McCrea and Gumbiner, 1991). Another Arm protein present in this cell-cell adhesion complex is p120ctn, which interacts with the cytoplasmic domain of E-cadherin but not with αE-catenin (Daniel and Reynolds, 1995; Reynolds et al., 1994). The p120ctn protein comprises 10 Arm repeats, while βcatenin and plakoglobin each comprise 12.5 Arm repeats. It serves as a prototype of a novel subfamily of Arm proteins (Reynolds and Daniel, 1997). Five proteins have already been described to share the p120ctn Arm repeat organization, namely plakophilin-1 (also known as ‘band 6 protein’ of bovine muzzle desmosome fractions; Heid et al., 1994; Schmidt et al., 1997), plakophilin-2 (Mertens et al., 1996), the ARVCF (Armadillo repeat gene deleted in velo cardio-facial syndrome) gene product (Sirotkin et al., 1997), p0071 (Hatzfeld and Nachtsheim, 1996), and δ-catenin, which is also known as the neural plakophilin-related arm-protein (NPRAP) (Paffenholz and Franke, 1997; Zhou et al., 1997). These proteins are generally expressed in a wide variety of cell types, except for δ-catenin/NPRAP, which is so far the only protein of this family displaying a restricted expression pattern, in this case neural tissue (Paffenholz and Franke, 1997). For several members of the p120ctn/plakophilin family a desmosomal localization has been shown. Desmosomes (maculae adhaerentes) are epithelial adhering junctions involved in cell-cell adhesion, differentiation and signal transduction (Bornslaeger et al., 1997; Hatzfeld, 1997). They are assembled on a scaffold of transmembrane glycoproteins 2265 Journal of Cell Science 112, 2265-2276 (1999) Printed in Great Britain © The Company of Biologists Limited 1999 JCS0355