Plakophilin-3, a novel Armadillo-like protein present in nuclei and desmosomes of epithelial cells

We report on a novel Armadillo-like protein, termed plakophilin-3, The huma n protein, which is encoded by a 2.8 kb messenger RNA, has a predicted mole cular mass of 87 kDa, The protein comprises 10 Armadillo-like repeats, prec eded by an amino-terminal region of 293 amino acid residues and followed by a short carboxy-terminal region of 27 amino acid residues. Plakophilin-3 i s classified as a member of the p120(ctn)/plakophilin subfamily of Armadill o proteins based on the number and organization of the Armadillo repeats an d its high sequence similarity to other members of this family. CLUSTAL W a lignment of p120(ctn)/plakophilin subfamily members showed the plakophilin- 3 protein to be most similar to plakophilin-1 and -2, Western blot analysis of plakophilin-3 revealed expression in all epithelial cell lines tested b ut not in foreskin fibroblasts and various sarcoma-derived cell lines. This is unlike most other members of the p120(ctn)/plakophilin subfamily, which are widely expressed, By immunofluorescence, the plakophilin-3 protein was colocalized with desmoglein in desmosomes of epithelial cells. In addition , an intriguing speckle-like nuclear staining was observed. Hence, like pla kophilin-1 and -2, plakophilin-3 displays a dual intracellular location, i. e. in the desmosomal plaque and in the nucleus. These results suggest the i nvolvement of plakophilin-3 in both desmosome-dependent adhesion and signal ing pathways. Furthermore, the human plakophilin-3 gene was mapped on the c hromosomal locus 11p15 by fluorescent in situ hybridization.