Transmembrane protein PERP is a component of tessellate junctions and of other junctional and non- junctional plasma membrane regions in diverse epithelial Citation

Protein PERP (p53 apoptosis effector related to PMP-22) is a small (21.4 kDa) transmembrane polypeptide with an amino acid sequence indicative of a tetraspanin character. It is enriched in the plasma membrane and apparently contributes to cell-cell contacts. Hitherto, it has been reported to be exclusively a component of desmosomes of some stratified epithelia. However, by using a allow us to localize PERP predominantly in small intradesmosomal locations and in variously sized, junction-like periand interdesmosomal regions (“tessellate junctions”), mostly in mosaic or amalgamated combinations with other molecules believed, to date, to be exclusive components of tight and adherens junctions. In the heart, PERP is a major component of the composite junctions of the intercalated disks connecting cardiomyocytes. Finally, protein PERP is a cobblestone-like general component of special plasma membrane regions such as the bile canaliculi of liver and subapical-to-lateral zones of diverse columnar epithelia and upper urothelial cell layers. We discuss possible organizational and architectonic functions of protein PERP and its potential value as an immunohistochemical diagnostic marker.

[1]  N. Frey,et al.  The plaque protein myozap identified as a novel major component of adhering junctions in endothelia of the blood and the lymph vascular systems , 2012, Journal of cellular and molecular medicine.

[2]  F. van Roy,et al.  Loss of αT-catenin alters the hybrid adhering junctions in the heart and leads to dilated cardiomyopathy and ventricular arrhythmia following acute ischemia , 2012, Journal of Cell Science.

[3]  A. Lichtenberg,et al.  The adhering junctions of valvular interstitial cells: molecular composition in fetal and adult hearts and the comings and goings of plakophilin-2 in situ, in cell culture and upon re-association with scaffolds , 2012, Cell and Tissue Research.

[4]  H. Vogel,et al.  Deficiency of the p53/p63 target Perp alters mammary gland homeostasis and promotes cancer , 2012, Breast Cancer Research.

[5]  S. Rickelt.  Plakophilin-2: a cell-cell adhesion plaque molecule of selective and fundamental importance in cardiac functions and tumor cell growth , 2012, Cell and Tissue Research.

[6]  N. Frey,et al.  Protein myozap — a late addition to the molecular ensembles of various kinds of adherens junctions , 2011, Cell and Tissue Research.

[7]  W. Franke,et al.  Mesenchymal–epithelial transitions: Spontaneous and cumulative syntheses of epithelial marker molecules and their assemblies to novel cell junctions connecting human hematopoietic tumor cells to carcinomatoid tissue structures , 2011, International journal of cancer.

[8]  M. Ott,et al.  E–N-cadherin heterodimers define novel adherens junctions connecting endoderm-derived cells , 2011, The Journal of cell biology.

[9]  W. Franke,et al.  Intercellular adhering junctions with an asymmetric molecular composition: desmosomes connecting Merkel cells and keratinocytes , 2011, Cell and Tissue Research.

[10]  L. Attardi,et al.  Desmosomes: new perpetrators in tumour suppression , 2011, Nature Reviews Cancer.

[11]  J. Svendsen,et al.  Screening of three novel candidate genes in arrhythmogenic right ventricular cardiomyopathy. , 2011, Genetic testing and molecular biomarkers.

[12]  D. Spiller,et al.  PERP expression stabilizes active p53 via modulation of p53-MDM2 interaction in uveal melanoma cells , 2011, Cell Death and Disease.

[13]  H. Vogel,et al.  Loss of the p53/p63 Regulated Desmosomal Protein Perp Promotes Tumorigenesis , 2010, PLoS genetics.

[14]  Rebecca A. Ihrie,et al.  Loss of the Desmosomal Component Perp Impairs Wound Healing In Vivo , 2010, Dermatology research and practice.

[15]  S. Rickelt.  The molecular and cell biological characterization of cell-cell junctions in mesenchymally derived cells and tissues , 2010 .

[16]  W. Franke,et al.  Upregulation of plakophilin‐2 and its acquisition to adherens junctions identifies a novel molecular ensemble of cell–cell‐attachment characteristic for transformed mesenchymal cells , 2009, International journal of cancer.

[17]  W. Franke,et al.  Discovering the molecular components of intercellular junctions--a historical view. , 2009, Cold Spring Harbor perspectives in biology.

[18]  L. Attardi,et al.  Differential PERP regulation by TP63 mutants provides insight into AEC pathogenesis , 2009, American journal of medical genetics. Part A.

[19]  D. Spiller,et al.  P53 apoptosis mediator PERP: localization, function and caspase activation in uveal melanoma , 2009, Journal of cellular and molecular medicine.

[20]  L. Attardi,et al.  Loss of the desmosomal protein perp enhances the phenotypic effects of pemphigus vulgaris autoantibodies. , 2009, The Journal of investigative dermatology.

[21]  A. Lichtenberg,et al.  Cordial connections: molecular ensembles and structures of adhering junctions connecting interstitial cells of cardiac valves in situ and in cell culture , 2009, Cell and Tissue Research.

[22]  A. Kowalczyk,et al.  The desmosome. , 2009, Cold Spring Harbor perspectives in biology.

[23]  Jun Dong,et al.  Preferential gene expression in the limbus of the vervet monkey , 2008, Molecular vision.

[24]  W. Peitsch,et al.  Subtypes of melanocytes and melanoma cells distinguished by their intercellular contacts: heterotypic adherens junctions, adhesive associations, and dispersed desmoglein 2 glycoproteins , 2008, Cell and Tissue Research.

[25]  D. Garrod,et al.  Desmosome structure, composition and function. , 2008, Biochimica et biophysica acta.

[26]  R. Moll,et al.  Endothelial and virgultar cell formations in the mammalian lymph node sinus: endothelial differentiation morphotypes characterized by a special kind of junction (complexus adhaerens) , 2008, Cell and Tissue Research.

[27]  J. Kartenbeck,et al.  Characterization of a novel type of adherens junction in meningiomas and the derived cell line HBL-52 , 2008, Cell and Tissue Research.

[28]  F. Braet,et al.  A unique and specific interaction between αT-catenin and plakophilin-2 in the area composita, the mixed-type junctional structure of cardiac intercalated discs , 2007, Journal of Cell Science.

[29]  C. Grund,et al.  The area composita of adhering junctions connecting heart muscle cells of vertebrates - III: assembly and disintegration of intercalated disks in rat cardiomyocytes growing in culture. , 2007, European journal of cell biology.

[30]  R. Windoffer,et al.  Structure and function of desmosomes. , 2007, International review of cytology.

[31]  I. Grierson,et al.  Expression of p53-induced apoptosis effector PERP in primary uveal melanomas: downregulation is associated with aggressive type. , 2006, Experimental eye research.

[32]  Rebecca A. Ihrie,et al.  Adult mice lacking the p53/p63 target gene Perp are not predisposed to spontaneous tumorigenesis but display features of ectodermal dysplasia syndromes , 2006, Cell Death and Differentiation.

[33]  C. Grund,et al.  The area composita of adhering junctions connecting heart muscle cells of vertebrates. I. Molecular definition in intercalated disks of cardiomyocytes by immunoelectron microscopy of desmosomal proteins. , 2006, European journal of cell biology.

[34]  Rebecca A. Ihrie,et al.  The requirement for perp in postnatal viability and epithelial integrity reflects an intrinsic role in stratified epithelia. , 2006, The Journal of investigative dermatology.

[35]  Rebecca A. Ihrie,et al.  Mice lacking the p53/p63 target gene Perp are resistant to papilloma development. , 2005, Cancer research.

[36]  Rebecca A. Ihrie,et al.  A New Perp in the Lineup: Linking p63 and Desmosomal Adhesion , 2005, Cell cycle.

[37]  Rebecca A. Ihrie,et al.  Perp Is a p63-Regulated Gene Essential for Epithelial Integrity , 2005, Cell.

[38]  L. Godsel,et al.  The molecular composition and function of desmosomes. , 2004, Handbook of experimental pharmacology.

[39]  Rebecca A. Ihrie,et al.  Perp Is a Mediator of p53-Dependent Apoptosis in Diverse Cell Types , 2003, Current Biology.

[40]  R. Moll,et al.  Tight junction-related structures in the absence of a lumen: occludin, claudins and tight junction plaque proteins in densely packed cell formations of stratified epithelia and squamous cell carcinomas. , 2003, European journal of cell biology.

[41]  Ingrid Moll,et al.  Tight junctions and compositionally related junctional structures in mammalian stratified epithelia and cell cultures derived therefrom. , 2002, European journal of cell biology.

[42]  W. Franke,et al.  Molecular Diversity of Plaques of Epithelial‐Adhering Junctions , 2000, Annals of the New York Academy of Sciences.

[43]  S. Lowe,et al.  PERP, an apoptosis-associated target of p53, is a novel member of the PMP-22/gas3 family. , 2000, Genes & development.

[44]  D. Schmitt,et al.  Interkeratinocyte adherens junctions: immunocytochemical visualization of cell-cell junctional structures, distinct from desmosomes, in human epidermis. , 1996, The Journal of investigative dermatology.

[45]  C. Grund,et al.  Continual assembly of half-desmosomal structures in the absence of cell contacts and their frustrated endocytosis: a coordinated Sisyphus cycle , 1995, The Journal of cell biology.

[46]  Y. Horiguchi,et al.  Ultrastructural localization of E-cadherin cell adhesion molecule on the cytoplasmic membrane of keratinocytes in vivo and in vitro. , 1994, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[47]  Wacker Hh.  Sinus lining cells. Immune accessory cells of lymph node sinuses , 1994 .

[48]  R. Briggaman,et al.  Adherens junctions: demonstration in human epidermis. , 1993, The Journal of investigative dermatology.

[49]  R. Duden,et al.  Organization of desmosomal plaque proteins in cells growing at low calcium concentrations , 1988, The Journal of cell biology.

[50]  C. Daniel,et al.  Postnatal Development of the Rodent Mammary Gland , 1987 .

[51]  E. Lane,et al.  Keratin Expression in the Mammary Gland , 1987 .

[52]  R. Hynes,et al.  Plakoglobin: A protein common to different kinds of intercellular adhering junctions , 1986, Cell.

[53]  P. Steart,et al.  Mouse antisera specific for desmosomal adhesion molecules of suprabasal skin cells, meninges, and meningioma. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[54]  J. Bereiter-Hahn,et al.  Biology of the integument. 2. Vertebrates. , 1986 .

[55]  J. Jorcano,et al.  Patterns of Expression and Organization of Cytokeratin Intermediate Filaments , 1985, Annals of the New York Academy of Sciences.

[56]  W. Franke,et al.  The complement of desmosomal plaque proteins in different cell types , 1985, The Journal of cell biology.

[57]  R. Moll,et al.  Vimentin filament-desmosome cytoskeleton of diverse types of human meningiomas. A distinctive diagnostic feature. , 1984, Laboratory investigation; a journal of technical methods and pathology.

[58]  R. Moll,et al.  Attachment of vimentin filaments to desmosomal plaques in human meningiomal cells and arachnoidal tissue , 1984, The Journal of cell biology.

[59]  N. Patel,et al.  Immunological comparison of desmosomal components from several bovine tissues , 1984, Journal of cellular biochemistry.

[60]  C. Grund,et al.  An epithelial cell line with elongated myoid morphology derived from bovine mammary gland. Expression of cytokeratins and desmosomal plaque proteins in unusual arrays. , 1983, Experimental cell research.

[61]  P. Cowin,et al.  Antibodies to epithelial desmosomes show wide tissue and species cross-reactivity , 1983, Nature.

[62]  W. Franke,et al.  Biochemical and immunological characterization of desmoplakins I and II, the major polypeptides of the desmosomal plaque. , 1983, Journal of molecular biology.

[63]  D. Skerrow,et al.  Tonofilament differentiation in human epidermis, isolation and polypeptide chain composition of keratinocyte subpopulations. , 1983, Experimental cell research.

[64]  B. Geiger,et al.  Different modes of internalization of proteins associated with adhaerens junctions and desmosomes: experimental separation of lateral contacts induces endocytosis of desmosomal plaque material. , 1982, The EMBO journal.

[65]  H. Denk,et al.  Differentiation-related patterns of expression of proteins of intermediate-size filaments in tissues and cultured cells. , 1982, Cold Spring Harbor symposia on quantitative biology.

[66]  H. Denk,et al.  Diversity of cytokeratins. Differentiation specific expression of cytokeratin polypeptides in epithelial cells and tissues. , 1981, Journal of molecular biology.

[67]  G. Gorbsky,et al.  Isolation of the intercellular glycoproteins of desmosomes , 1981, The Journal of cell biology.

[68]  J. Vandekerckhove,et al.  Permanently proliferating rat vascular smooth muscle cell with maintained expression of smooth muscle characteristics, including actin of the vascular smooth muscle type , 1980, The Journal of cell biology.

[69]  T. W. Keenan,et al.  Intermediate-sized filaments of the prekeratin type in myoepithelial cells , 1980, The Journal of cell biology.

[70]  K. Weber,et al.  Widespread occurrence of intermediate-sized filaments of the vimentin-type in cultured cells from diverse vertebrates. , 1979, Experimental cell research.

[71]  T. W. Keenan,et al.  Structure and biochemical composition of desmosomes and tonofilaments isolated from calf muzzle epidermis , 1978, The Journal of cell biology.

[72]  A. Matoltsy,et al.  ISOLATION OF EPIDERMAL DESMOSOMES , 1974, The Journal of cell biology.

[73]  B. Ketterer,et al.  The ultrastructure and chemistry of the luminal plasma membrane of the mammalian urinary bladder: a structure with low permeability to water and ions. , 1974, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[74]  L. Staehelin,et al.  Structure and function of intercellular junctions. , 1974, International review of cytology.

[75]  G. Palade,et al.  JUNCTIONAL COMPLEXES IN VARIOUS EPITHELIA , 1963, The Journal of cell biology.