Plakophilins 2a and 2b: constitutive proteins of dual location in the karyoplasm and the desmosomal plaque.

Abstract

Abstract. Using antibodies and recombinant DNA techniques, we have identified plakophilin 2, a novel desmosomal plaque protein of Mr 100,000 (estimated from SDS-PAGE), which is a member of the arm-repeat family of proteins and can occur in two splice forms (2a and 2b) because of the insertion of a 44 amino acid (aa)-encoding exon. In its aa sequence (837 and 881 aa, calculated pls: 9.33 and 9.38, mol wts 92,750 and 97,410 kD), it is conspicuously related to the 80-kD plakophilin 1, with which it shares a central region of 9 repeats of the arm-motif, preceeded by a long head region and followed by a very short (11 aa) carboxy-terminal sequence. Plakophilin 2 and its mRNA have been detected in a wide range of tissues and cell types, including cells devoid of desmosomes. By light and electron microscopical immunolocalization, plakophilin 2 has been localized to plaques of desmosomes of onelayered ("simple") and complex epithelia, carcinomas, diverse epithelium-derived cell culture lines, as well as cardiac tissue and the dendritic reticulum cells of lymphatic germinal centers, i.e., desmosomes in which plakophilin 1 is not detected. However, plakophilin 2 has also been localized in the desmosomes of certain but not all stratified epithelia where it coexists with plakophilin 1. Remarkably, plakophilin 2 is also enriched in the karyoplasm of a wide range of cell types, including many that lack desmosomes and in which, therefore, the nuclear state is the only locally enriched form of plakophilin 2 present. We conclude that plakophilins 2a and 2b are basic nuclear proteins that in certain cell types additionally assemble with other proteins to form the desmosomal plaque and serve general nuclear functions as well as a function specific to many but not all desmosomes.oN6 the diverse forms of plaque-coated adhering junctions (12; for reviews see references 66, 72), the desmosomes are a particularly well-defined category: They represent clusters of certain isoforms of two types of transmembrane glycoproteins, the desmogleins (Dsgl-3) and desmocollins (Dscl-3), members of the larger cadherin family of cell adhesion molecules, which at their carboxy-terminal cytoplasmic portions assemble the common plaque protein, plakoglobin, and several desmosome-specific proteins. These include general desmosome components such as desmoplakin I and cell type-specific proteins such as desmoplakin II and plakophilin 1 (originally identified as "band-6-protein" of desmosomal fractions from bovine muzzle; for references see 10,21,26,32,68). One of the desmosomal plaque proteins, plakoglobin, which has also been shown to occur in nondesmosomal adhering junctions (8,17,18) and in a soluble cytoplasmic pool (30), has been identified, on the basis of its amino acid (aa) 1 sequence (13, 19), as a member of a group of proteins characterized by variable numbers of repeats of a motif of ,-~42 aa, the so-called arm-repeats first identified in the developmentally defined gene armadillo of Drosophila (58; for references see 57,59,66). This armrepeat pr...

Mutations in the desmosomal protein plakophilin-2 are common in arrhythmogenic right ventricular cardiomyopathy

“…At least three groups of molecules contribute to the formation of desmosomes: desmosomal cadherins, armadillo-repeat proteins and plakins 7 . The plakophilins, which are armadillo-related proteins, contain ten 42-amino acid armadillorepeat motifs and are located in the outer dense plaque of desmosomes linking desmosomal cadherins with desmoplakin and the intermediate filament system 8 . Like other armadillo-repeat proteins, plakophilins are also found in the nucleus, where they may have a role in transcriptional regulation 9 .…”

“…Like other armadillo-repeat proteins, plakophilins are also found in the nucleus, where they may have a role in transcriptional regulation 9 . Plakophilin-2 exists in two alternatively spliced isoforms (2a and 2b), interacts with multiple other cell adhesion proteins and is the primary cardiac plakophilin 8,10 .…”

E‐cadherin is a selective and strongly dominant prognostic factor in squamous cell carcinoma: A comparison of E‐cadherin with desmosomal components

“…For dg (c), this association was much weaker, and for dp (b) no such correlation was found. d, survival rates in stage IV tumors in relation to ecad protein scores (Ͻ5 vs. [5][6][7][8]. Note that ecad was a strong prognostic marker of stage IV tumors.…”

“…The "classical" E-cadherin (ecad) maintains intercellular adhesion in the adhaerens junction, and the desmogleins (dg) and desmocollins (dc) are the principal cadherins of the desmosomes. [3][4][5][6][7][8][9][10][11][12][13] Regarding adhaerens junctions, numerous studies have shown that loss of adhesion can be caused by deletions or mutations, 14 -17 silencing by CpG methylation 18 -20 or otherwise altered gene expression, resulting in loss or reduction of protein staining of 1 of the proteins involved in junction formation [21][22][23] ; (for reviews, see references 24,25). From these studies, it was concluded that alteration of cellular adhesion may lead to dedifferentiation, tumorigenesis and metastasis.…”

A Novel Helicase-Type Protein in the Nucleolus: Protein NOH61

“…In the experiments reported here, antibodies NOH61-2.1 and NOH61-5.1 directed against the peptide sequences GPKGDKASDPEAGV (aa 332-345) and EKLKTYFEDNPRDLQ (aa 458 -472), respectively, were routinely used after affinity purification on iodoacetyl-immobilized peptide (Mertens et al, 1996). Antibody NOH61-4.2 (aa 23-36; TDL-GWSRPTLIQEK) showed the same specificities.…”