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PMID: 19674883 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Plakophilins: multifunctional scaffolds for adhesion and signaling.

Current opinion in cell biology ·Vol. 21 ·No. 5 ·2009-10-00 ·Pages 708-16

Bass-Zubek AE, Godsel LM, Delmar M, Green KJ

Abstract

Armadillo family proteins known as plakophilins have been characterized as structural components of desmosomes that stabilize and strengthen adhesion by enhancing attachments with the intermediate filament cytoskeleton. However, plakophilins and their close relatives are emerging as versatile scaffolds for multiple signaling and metabolic processes that not only facilitate junction dynamics but also more globally regulate diverse cellular activities. While perturbation of plakophilin functions contribute to inherited diseases and cancer pathogenesis, the functional significance of the multiple PKP isoforms and the mechanisms by which their behaviors are regulated remain to be elucidated.

MeSH Terms
Animals Cell Adhesion Disease Susceptibility/metabolism Humans Neoplasms/metabolism Plakophilins/chemistry,metabolism Signal Transduction Stress, Physiological
Chemicals
Plakophilins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Bass-Zubek Amanda E
Department of Pathology, Northwestern University Feinberg School of Medicine, 303 E. Chicago Avenue, Chicago, IL 60611, USA.
Godsel Lisa M
Delmar Mario
Green Kathleen J
References (67)
67 references, click to expand
  1. Defining desmosomal plakophilin-3 interactions.
    J Cell Biol. 2003 Apr 28;161(2):403-16 PMID: 12707304
  2. Decreased plakophilin-1 expression promotes increased motility in head and neck squamous cell carcinoma cells.
    Cell Commun Adhes. 2007 Mar-Jun;14(2-3):99-109 PMID: 17668353
  3. Immunohistochemical localization of plakophilins (PKP1, PKP2, PKP3, and p0071) in primary oropharyngeal tumors: correlation with clinical parameters.
    Hum Pathol. 2003 Jun;34(6):565-72 PMID: 12827610
  4. The distribution of the desmosomal protein, plakophilin 1, in human skin and skin tumors.
    J Invest Dermatol. 1997 Feb;108(2):139-46 PMID: 9008225
  5. Characterization of the molecular phenotype of two arrhythmogenic right ventricular cardiomyopathy (ARVC)-related plakophilin-2 (PKP2) mutations.
    Heart Rhythm. 2008 Dec;5(12):1715-23 PMID: 19084810
  6. Suppression of canonical Wnt/beta-catenin signaling by nuclear plakoglobin recapitulates phenotype of arrhythmogenic right ventricular cardiomyopathy.
    J Clin Invest. 2006 Jul;116(7):2012-21 PMID: 16823493
  7. Comparative analysis of armadillo family proteins in the regulation of a431 epithelial cell junction assembly, adhesion and migration.
    J Invest Dermatol. 2004 Sep;123(3):426-33 PMID: 15304078
  8. Plakophilin 2: a critical scaffold for PKC alpha that regulates intercellular junction assembly.
    J Cell Biol. 2008 May 19;181(4):605-13 PMID: 18474624
  9. Desmosomal plakophilin 2 as a differentiation marker in normal and malignant tissues.
    Differentiation. 1999 Jun;64(5):277-90 PMID: 10374264
  10. The function of plakophilin 1 in desmosome assembly and actin filament organization.
    J Cell Biol. 2000 Apr 3;149(1):209-22 PMID: 10747098
  11. The alpha isoform of protein kinase C is involved in signaling the response of desmosomes to wounding in cultured epithelial cells.
    Mol Biol Cell. 2000 Mar;11(3):1077-92 PMID: 10712521
  12. Plakophilins 2a and 2b: constitutive proteins of dual location in the karyoplasm and the desmosomal plaque.
    J Cell Biol. 1996 Nov;135(4):1009-25 PMID: 8922383
  13. Plakophilin-2 mutations are the major determinant of familial arrhythmogenic right ventricular dysplasia/cardiomyopathy.
    Circulation. 2006 Apr 4;113(13):1650-8 PMID: 16567567
  14. Intermediate filament-membrane attachments function synergistically with actin-dependent contacts to regulate intercellular adhesive strength.
    J Cell Biol. 2002 Dec 23;159(6):1005-17 PMID: 12499357
  15. Regulation of cadherin stability and turnover by p120ctn: implications in disease and cancer.
    Semin Cell Dev Biol. 2004 Dec;15(6):657-63 PMID: 15561585
  16. Protein kinase C activation upregulates intercellular adhesion of alpha-catenin-negative human colon cancer cell variants via induction of desmosomes.
    J Cell Biol. 1997 Jun 2;137(5):1103-16 PMID: 9166410
  17. Regulation of cadherin trafficking.
    Traffic. 2009 Mar;10(3):259-67 PMID: 19055694
  18. Identification of the junctional plaque protein plakophilin 3 in cytoplasmic particles containing RNA-binding proteins and the recruitment of plakophilins 1 and 3 to stress granules.
    Mol Biol Cell. 2006 Mar;17(3):1388-98 PMID: 16407409
  19. Nuclear particles containing RNA polymerase III complexes associated with the junctional plaque protein plakophilin 2.
    Proc Natl Acad Sci U S A. 2001 Jul 3;98(14):7795-800 PMID: 11416169
  20. ERBIN associates with p0071, an armadillo protein, at cell-cell junctions of epithelial cells.
    Genes Cells. 2002 May;7(5):475-85 PMID: 12047349
  21. P120 catenin is associated with desmogleins when desmosomes are assembled in high-Ca2+ medium but not when disassembled in low-Ca2+ medium in DJM-1 cells.
    J Dermatol. 2008 Jun;35(6):317-24 PMID: 18578707
  22. Functional analysis of C-TAK1 substrate binding and identification of PKP2 as a new C-TAK1 substrate.
    EMBO J. 2003 Sep 1;22(17):4431-42 PMID: 12941695
  23. p120-catenin mediates inflammatory responses in the skin.
    Cell. 2006 Feb 10;124(3):631-44 PMID: 16469707
  24. Spatiotemporal development and distribution of intercellular junctions in adult rat cardiomyocytes in culture.
    Circ Res. 1999 Jul 23;85(2):154-67 PMID: 10417397
  25. The area composita of adhering junctions connecting heart muscle cells of vertebrates - IV: coalescence and amalgamation of desmosomal and adhaerens junction components - late processes in mammalian heart development.
    Eur J Cell Biol. 2007 Jul;86(7):377-91 PMID: 17532539
  26. p120-ctn: A nexus for contextual signaling via Rho GTPases.
    Biochim Biophys Acta. 2007 Jan;1773(1):34-46 PMID: 17028013
  27. Desmoplakin is essential in epidermal sheet formation.
    Nat Cell Biol. 2001 Dec;3(12):1076-85 PMID: 11781569
  28. Remodeling of myocyte gap junctions in arrhythmogenic right ventricular cardiomyopathy due to a deletion in plakoglobin (Naxos disease).
    Heart Rhythm. 2004 May;1(1):3-11 PMID: 15851108
  29. Plakophilin-3-deficient mice develop hair coat abnormalities and are prone to cutaneous inflammation.
    J Invest Dermatol. 2008 Jun;128(6):1375-85 PMID: 18079750
  30. Requirement of plakophilin 2 for heart morphogenesis and cardiac junction formation.
    J Cell Biol. 2004 Oct 11;167(1):149-60 PMID: 15479741
  31. Plakophilins: Multifunctional proteins or just regulators of desmosomal adhesion?
    Biochim Biophys Acta. 2007 Jan;1773(1):69-77 PMID: 16765467
  32. A unique and specific interaction between alphaT-catenin and plakophilin-2 in the area composita, the mixed-type junctional structure of cardiac intercalated discs.
    J Cell Sci. 2007 Jun 15;120(Pt 12):2126-36 PMID: 17535849
  33. The armadillo protein p0071 regulates Rho signalling during cytokinesis.
    Nat Cell Biol. 2006 Dec;8(12):1432-40 PMID: 17115030
  34. Plakophilin-3, a novel armadillo-like protein present in nuclei and desmosomes of epithelial cells.
    J Cell Sci. 1999 Jul;112 ( Pt 14):2265-76 PMID: 10381383
  35. Dependence of electrical coupling on mechanical coupling in cardiac myocytes: insights gained from cardiomyopathies caused by defects in cell-cell connections.
    Ann N Y Acad Sci. 2005 Jun;1047:336-44 PMID: 16093509
  36. 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.
    Eur J Cell Biol. 2006 Feb;85(2):69-82 PMID: 16406610
  37. Structure of the armadillo repeat domain of plakophilin 1.
    J Mol Biol. 2005 Feb 11;346(1):367-76 PMID: 15663951
  38. Protein p0071 - an armadillo plaque protein that characterizes a specific subtype of adherens junctions.
    J Cell Sci. 2009 Jan 1;122(Pt 1):21-4 PMID: 19092057
  39. Plakophilin 3--a novel cell-type-specific desmosomal plaque protein.
    Differentiation. 1999 Jun;64(5):291-306 PMID: 10374265
  40. Protein binding and functional characterization of plakophilin 2. Evidence for its diverse roles in desmosomes and beta -catenin signaling.
    J Biol Chem. 2002 Mar 22;277(12):10512-22 PMID: 11790773
  41. Targeting of p0071 to desmosomes and adherens junctions is mediated by different protein domains.
    J Cell Sci. 2003 Apr 1;116(Pt 7):1219-33 PMID: 12615965
  42. The transcription factor ZEB1 (deltaEF1) represses Plakophilin 3 during human cancer progression.
    FEBS Lett. 2007 Apr 17;581(8):1617-24 PMID: 17391671
  43. PAPIN. A novel multiple PSD-95/Dlg-A/ZO-1 protein interacting with neural plakophilin-related armadillo repeat protein/delta-catenin and p0071.
    J Biol Chem. 2000 Sep 22;275(38):29875-80 PMID: 10896674
  44. Desmoplakin assembly dynamics in four dimensions: multiple phases differentially regulated by intermediate filaments and actin.
    J Cell Biol. 2005 Dec 19;171(6):1045-59 PMID: 16365169
  45. The Erbin PDZ domain binds with high affinity and specificity to the carboxyl termini of delta-catenin and ARVCF.
    J Biol Chem. 2002 Apr 12;277(15):12906-14 PMID: 11821434
  46. Localization of p0071-interacting proteins, plakophilin-related armadillo-repeat protein-interacting protein (PAPIN) and ERBIN, in epithelial cells.
    Oncogene. 2002 Oct 10;21(46):7042-9 PMID: 12370826
  47. Targeting of p0071 to the midbody depends on KIF3.
    J Cell Sci. 2009 Apr 15;122(Pt 8):1174-83 PMID: 19339549
  48. Plakophilin3 downregulation leads to a decrease in cell adhesion and promotes metastasis.
    Int J Cancer. 2008 Nov 15;123(10):2303-14 PMID: 18729189
  49. The intercalated disk as a single functional unit.
    Heart Rhythm. 2004 May;1(1):12-3 PMID: 15851109
  50. Plakophilin 1 interferes with plakoglobin binding to desmoplakin, yet together with plakoglobin promotes clustering of desmosomal plaque complexes at cell-cell borders.
    J Cell Sci. 2001 Feb;114(Pt 4):727-38 PMID: 11171378
  51. Anchorage of microtubule minus ends to adherens junctions regulates epithelial cell-cell contacts.
    Cell. 2008 Nov 28;135(5):948-59 PMID: 19041755
  52. Interaction of plakophilins with desmoplakin and intermediate filament proteins: an in vitro analysis.
    J Cell Sci. 2000 Jul;113 ( Pt 13):2471-83 PMID: 10852826
  53. The Armadillo family protein p0071 is a VE-cadherin- and desmoplakin-binding protein.
    J Biol Chem. 2003 Jan 17;278(3):1774-83 PMID: 12426320
  54. Microtubules and cadherins: a neglected partnership.
    Front Biosci (Landmark Ed). 2009 Jan 01;14:3159-67 PMID: 19273264
  55. The head domain of plakophilin-1 binds to desmoplakin and enhances its recruitment to desmosomes. Implications for cutaneous disease.
    J Biol Chem. 1999 Jun 25;274(26):18145-8 PMID: 10373410
  56. Mutations in the plakophilin 1 gene result in ectodermal dysplasia/skin fragility syndrome.
    Nat Genet. 1997 Oct;17(2):240-4 PMID: 9326952
  57. The area composita of adhering junctions connecting heart muscle cells of vertebrates. V. The importance of plakophilin-2 demonstrated by small interference RNA-mediated knockdown in cultured rat cardiomyocytes.
    Eur J Cell Biol. 2008 Jul;87(7):399-411 PMID: 18261826
  58. p120 catenin associates with microtubules: inverse relationship between microtubule binding and Rho GTPase regulation.
    J Biol Chem. 2004 Feb 20;279(8):6588-94 PMID: 14660598
  59. Carboxyl terminus of Plakophilin-1 recruits it to plasma membrane, whereas amino terminus recruits desmoplakin and promotes desmosome assembly.
    J Biol Chem. 2006 Jun 23;281(25):16962-16970 PMID: 16632867
  60. Lack of plakophilin 1 increases keratinocyte migration and reduces desmosome stability.
    J Cell Sci. 2003 Aug 15;116(Pt 16):3303-14 PMID: 12840072
  61. De novo formation of desmosomes in cultured cells upon transfection of genes encoding specific desmosomal components.
    Exp Cell Res. 2003 Apr 15;285(1):114-30 PMID: 12681292
  62. A new diagnostic test for arrhythmogenic right ventricular cardiomyopathy.
    N Engl J Med. 2009 Mar 12;360(11):1075-84 PMID: 19279339
  63. Mutations in the desmosomal protein plakophilin-2 are common in arrhythmogenic right ventricular cardiomyopathy.
    Nat Genet. 2004 Nov;36(11):1162-4 PMID: 15489853
  64. Plakophilin 3 oncogene as prognostic marker and therapeutic target for lung cancer.
    Cancer Res. 2005 Aug 15;65(16):7102-10 PMID: 16103059
  65. Plakophilins 1a and 1b: widespread nuclear proteins recruited in specific epithelial cells as desmosomal plaque components.
    Cell Tissue Res. 1997 Dec;290(3):481-99 PMID: 9369526
  66. Connexin43 remodeling caused by inhibition of plakophilin-2 expression in cardiac cells.
    Circ Res. 2007 Sep 28;101(7):703-11 PMID: 17673670
  67. Cell type-specific desmosomal plaque proteins of the plakoglobin family: plakophilin 1 (band 6 protein).
    Differentiation. 1994 Dec;58(2):113-31 PMID: 7890138
Article Info
Journal
Current opinion in cell biology
Abbr.
Curr Opin Cell Biol
ISSN
1879-0410
DOI
10.1016/j.ceb.2009.07.002
Published
2009-10-00
Epub
2009-00-10
Pages
708-16
Language
English
Region
England
NLM ID
8913428
PMCID
PMC3091506
Subset
IM
Grants
NIAMS NIH HHS · R01 AR 41836 · United States
NIAMS NIH HHS · R01 AR041836-15 · United States
NIAMS NIH HHS · R01 AR043380-13 · United States
NIAMS NIH HHS · R01 AR043380 · United States
NIAMS NIH HHS · R01 AR043380-12 · United States
NCI NIH HHS · R01 CA122151 · United States
NIAMS NIH HHS · R01 AR041836 · United States
NCI NIH HHS · R01 CA 122151 · United States
NCI NIH HHS · T32 CA009560 · United States
NCI NIH HHS · R01 CA122151-02 · United States
NHLBI NIH HHS · HL 087226 · United States
NCI NIH HHS · R01 CA122151-04 · United States
NCI NIH HHS · R01 CA122151-01 · United States
NHLBI NIH HHS · P01 HL087226 · United States
NIAMS NIH HHS · R01 AR041836-14 · United States
NIAMS NIH HHS · R01 AR041836-16 · United States
NCI NIH HHS · R01 CA122151-03 · United States
NIAMS NIH HHS · R01 AR 43380 · United States
NIAMS NIH HHS · R01 AR041836-17 · United States
NIAMS NIH HHS · R01 AR043380-11 · United States
NCI NIH HHS · T32 CA 009560 · United States
External Links
PubMed source DOI: 10.1016/j.ceb.2009.07.002 PMC Full Text View journal details
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