Elsevier

Differentiation

Volume 58, Issue 2, January 1995, Pages 113-131
Differentiation

Cell type-specific desmosomal plaque proteins of the plakoglobin family: plakophilin 1 (band 6 protein)

https://doi.org/10.1046/j.1432-0436.1995.5820113.xGet rights and content

Abstract

Desmosomes represent a special type of the plaque-bearing adhering junctions, characteristic of certain pathways of cell differentiation, which compositionally are not identical in the various kinds of desmosome-forming cells. While all desmosomes contain the cytoplasmic plaque proteins desmoplakin I and plakoglobin, they can vary in their specific complement of desmosomal cadherins and by the presence of additional plaque proteins. We have raised monoclonal antibodies recognizing one such ‘accessory’ plaque protein, the cytokeratin-binding, basic protein plakophilin 1, originally introduced as ‘band 6 protein’ or ‘polypeptide D6’, which is an abundant desmosomal component in certain epithelia. Using such antibodies, we have isolated cDNA clones encoding the bovine and the human protein and determined their complete amino acid sequences. The mRNAs, which on Northern blot tests appear as two bands corresponding to approximately 4 and 2.4 kb (bovine) or 5 and 2.6 kb (human), code for 727 amino acids (calculated mol. wt. 80,180; IEP 9.25) in bovine and 726 amino acids (mol. wt. 80,496; IEP 9.34) in human plakophilin. Sequence analyses have revealed the presence of 9.2 repeated units of the arm-motif sequence, confirming our previous conclusion that this protein is a member of a larger family of proteins including, inter alia, several membrane-associated plaque proteins such as vertebrate plakoglobin and β-catenin as well as the product of the armadillo gene of Drosophila. The plakophilin antibodies and cDNA probes have also allowed us to examine its synthesis in various tissues and cell cultures. While we confirm the occurrence of the protein in cytoskeletal fractions from various stratified squamous, complex, glandular duct and bladder epithelia, where it can be localized to desmosomes, we have, surprisingly, also identified the protein, although at lower amounts, in cytoskeletal fractions from several cultured cell lines in which the protein has not been consistently localized to desmosomes by immunofluorescence microscopy. Examples include cultured cells derived from certain simple epithelia such as the kidney-derived line MDBK and cultured calf lens cells. We have also found that, in all plakophilin 1-positive cells examined, a pool of diffusible (‘soluble’) cytoplasmic plakophilin exists, including cell lines such as human mammary carcinoma MCF-7 cells in which this soluble plakophilin seems to be the only detectable form. In addition, we have identified some soluble proteins conspicuously cross-reacting with plakophilin 1. Possible functions of plakophilin and its potential value as a marker for specific states of cell differentiation are discussed, particularly with respect to tumor diagnosis.

References (118)

  • BM Gumbiner

    Proteins associated with the cytoplasmic surface of adhesion molecules

    Neuron

    (1993)
  • K Hatta et al.

    Spatial and temporal expression pattern of N-cadherin cell adhesion molecules correlated with morphogenetic processes of chicken embryos

    Dev Biol

    (1987)
  • HW Heid et al.

    Patterns of expression of trichocytic and epithelial cytokeratins in mammalian tissues. II. Concomitant and mutually exclusive synthesis of trichocytic and epithelial cytokeratins in diverse human and bovine tissues (hair follicle, nail bed and matrix, lingual papilla, thymic reticulum)

    Differentiation

    (1988)
  • K Hiraoka et al.

    Both stimulatory and inhibitory GDP/GTP exchange proteins, smgGDS and rhoGDI, are active on multiple small GTP-binding proteins

    Biophys Res Commun

    (1992)
  • J Hülsken et al.

    Tumor-suppressor gene products in cell contacts: the cadherin-APC-armadillo connection

    Curr Opin Cell Biol

    (1994)
  • MW Hunkapiller et al.

    Isolation of microgram quantities of proteins from PAGE for amino acid sequence analysis

    Methods Enzymol

    (1983)
  • R Kemler

    Classical cadherins

    Semin Cell Biol

    (1992)
  • IA King et al.

    Expression of distinct desmocollin isoforms in human epidermis

    J Invest Dermatol

    (1993)
  • C Kintner

    Regulation of embryonic cell adhesion by the cadherin cytoplasmic domain

    Cell

    (1992)
  • PJ Koch et al.

    Desmosomal cadherins: another growing multigene family of adhesion molecules

    Curr Opin Cell Biol

    (1994)
  • J Kyhse-Andersen

    Electroblotting of multiple gels: a simple apparatus without buffer tank for rapid transfer of proteins from polyacrylamide to nitrocellulose

    J Biochem Biophys Methods

    (1984)
  • L Langbein et al.

    Molecular characterization of the body site-specific human epidermal cytokeratin 9: cDNA cloning, amino acid sequence, and tissue specificity of gene expression

    Differentiation

    (1993)
  • M Mathur et al.

    Interactions of the cytoplasmic domain of the desmosomal cadherin Dsg 1 with plakoglobin

    J Biol Chem

    (1994)
  • R Moll et al.

    The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells

    Cell

    (1982)
  • R Moll et al.

    The human gene encoding cytokeratin 20 and its expression during fetal development and in gastrointestinal carcinomas

    Differentiation

    (1993)
  • PZ O'Farrell et al.

    High resolution two-dimensional electrophoresis of basic as well as acidic proteins

    Cell

    (1977)
  • M Peifer et al.

    The segment polarity gene armadillo encodes an evolutionary conserved and functional modular protein that is the Drosophila homolog of human plakoglobin

    Cell

    (1990)
  • M Peifer et al.

    A repeating amino acid motif shared by proteins with diverse cellular roles

    Cell

    (1994)
  • FCS Ramaekers et al.

    Identification of the cytoskeletal proteins in lens-forming cells, a special epithelioid cell type

    Exp Cell Res

    (1980)
  • S Schäfer et al.

    Identification of the ubiquitous human desmoglein, Dsg2, and the expression catalogue of the desmoglein subfamily of desmosomal cadherins

    Exp Cell Res

    (1994)
  • M Schmelz et al.

    Complexus adhaerentes, a new group of desmoplakin-containing junctions in endothelial cells: II. Different types of lymphatic vessels

    Differentiation

    (1994)
  • LA Staehelin

    Structure and function of intercellular junctions

    Int Rev Cytol

    (1974)
  • T Achtstätter et al.

    Separation of cytokeratin polypeptides by gel electrophoretic and chromatographic techniques and their identification by immunoblotting

    Methods Enzymol

    (1986)
  • BD Angst et al.

    Desmoplakin II expression is not restricted to stratified epithelia

    J Cell Sci

    (1990)
  • J Arnemann et al.

    Stratification related expression of isoforms of the desmosomal cadherins in human epidermis

    J Cell Sci

    (1993)
  • KD Belanger et al.

    Genetic and physical interactions between Srp1p and nuclear pore complex proteins Nup1p and Nup2p

    J Cell Biol

    (1994)
  • S Butz et al.

    Plakoglobin and β-catenin: distinct but closely related

    Science

    (1992)
  • RS Buxton et al.

    Nomenclature of the desmosomal cadherins

    J Cell Biol

    (1993)
  • JM Chirgwin et al.

    Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease

    Biochemistry

    (1979)
  • P Cowin et al.

    The desmosome-intermediate filament complex

  • P Cowin et al.

    The complement of desmosomal plaque proteins in different cell types

    J Cell Biol

    (1985)
  • D Drenckhahn et al.

    Stress fibers in splenic sinus endothelium in situ: molecular structure, relationship to the extracellular matrix, and contractility

    J Cell Biol

    (1986)
  • P Drochmans et al.

    Structure and biochemical composition of desmosomes and tonofilaments isolated from calf muzzle epidermis

    J Cell Biol

    (1978)
  • C Eckerskorn et al.

    Internal amino acid sequence analysis of proteins separated by gel electrophoresis after tryptic digestion in polyacrylamide matrix

    Chromatographia

    (1989)
  • M Farquhar et al.

    Junctional complexes in various epithelia

    J Cell Biol

    (1963)
  • RM Fourney et al.

    Northern blotting: Efficient RNA staining and transfer

    Focus

    (1988)
  • WW Franke et al.

    Differentiation-related patterns of expression of proteins of intermediate-size filaments in tissues and cultured cells

    Cold Spring Harb Symp Quant Biol

    (1982)
  • WW Franke et al.

    Isolation and symmetrical splitting of desmosomal structures in 9 M urea

    Eur J Cell Biol

    (1983)
  • WW Franke et al.

    Significance of two desmosome plaque-associated polypeptides of molecular weights 75,000 and 83,000

    EMBO J

    (1983)
  • WW Franke et al.

    Change of cytokeratin filament organization during the cell cycle: selective masking of an immunologic determinant in interphase PtK2 cells

    J Cell Biol

    (1983)
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