Plakophilin 3 - a novel cell-type-specific desmosomal plaque protein

Desomosomes are cell-cell adhesion structures of epithelia and some non-epi thelial tissues, such as heart muscle and the dendritic reticulum of lymph node follicles, which on their cytoplasmic side anchor intermediate filamen ts at the plasma membrane. Besides clusters of specific transmembrane glyco proteins of the cadherin family (desmogleins and desmocollins), they contai n several desmosomal plaque proteins, such as desmoplakins, plakoglobin, an d one or more plakophilins. Using recombinant DNA and immunological techniq ues, we have identified a novel desmosomal plaque protein that is closely r elated to plakophilins 1 and 2, both members of the "armadillo-repeat" mult igene family, and have named it plakophilin 3 (PKP3). The product of the co mplete human cDNA defines a protein of 797 amino acids, with a calculated m olecular weight of 87.081 kDa and an isoelectric point of pH 10.1. Northern blot analysis has shown that PKP3 mRNA has a size of approximately 2.9 kb and is detectable in the total RNA of cells of stratified and single-layere d epithelia. With the help of specific poly- and monoclonal antibodies we h ave localized PKP3, by immunofluorescence or immunoelectron microscopy, to desmosomes of most simple and almost all stratified epithelia and cell line s derived therefrom, with the remarkable exception of hepatocytes and hepat ocellular carcinoma cells. We have also determined the structure of the hum an PKP3 gene and compared it with that of plakophilin 1 (PKP1). Using fluor escence in situ hybridization, we have localized the human genes for the th ree known plakophilins to the chromosomes 1q32 (PKP1), 12p11 (PKP2) and 11p 15 (PKP3). The similarities and differences of the diverse plakophilins are discussed.