Home LiteratureArticle Details
PMID: 23891292 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Desmosome assembly and dynamics.

Trends in cell biology ·Vol. 23 ·No. 11 ·2013-11-00 ·Pages 537-46

Nekrasova O, Green KJ

Abstract

Desmosomes are intercellular junctions that anchor intermediate filaments (IFs) to the plasma membrane, forming a supracellular scaffold that provides mechanical resilience to tissues. This anchoring function is accomplished by specialized members of the cadherin family and associated cytoskeletal linking proteins, which together form a highly organized membrane core flanked by mirror-image cytoplasmic plaques. Due to the biochemical insolubility of desmosomes, the mechanisms that govern assembly of these components into a functional organelle remained elusive. Recently developed molecular reporters and live cell imaging approaches have provided powerful new tools to monitor this finely tuned process in real time. Here we discuss studies that are beginning to decipher the machinery and regulation governing desmosome assembly and homeostasis in situ and how these mechanisms are affected during disease pathogenesis.

Keywords
armadillo proteins cell junctions desmoplakin desmosomal cadherins
MeSH Terms
Adherens Junctions/chemistry,metabolism Animals Desmosomes/chemistry,metabolism Homeostasis Humans
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Nekrasova Oxana
Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Green Kathleen J
References (87)
87 references, click to expand
  1. Desmoglein as a target in skin disease and beyond.
    J Invest Dermatol. 2012 Mar;132(3 Pt 2):776-84 PMID: 22189787
  2. The desmosome.
    Cold Spring Harb Perspect Biol. 2009 Aug;1(2):a002543 PMID: 20066089
  3. Desmosome assembly and cell-cell adhesion are membrane raft-dependent processes.
    J Biol Chem. 2011 Jan 14;286(2):1499-507 PMID: 21071449
  4. 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
  5. The DSPII splice variant is crucial for desmosome-mediated adhesion in HaCaT keratinocytes.
    J Cell Sci. 2012 Jun 15;125(Pt 12):2853-61 PMID: 22454510
  6. The calcium ATPase SERCA2 regulates desmoplakin dynamics and intercellular adhesive strength through modulation of PKCα signaling.
    FASEB J. 2011 Mar;25(3):990-1001 PMID: 21156808
  7. Hyper-adhesion in desmosomes: its regulation in wound healing and possible relationship to cadherin crystal structure.
    J Cell Sci. 2005 Dec 15;118(Pt 24):5743-54 PMID: 16303847
  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. Darier disease : a disease model of impaired calcium homeostasis in the skin.
    Biochim Biophys Acta. 2011 May;1813(5):1111-7 PMID: 21167218
  10. Plakoglobin rescues adhesive defects induced by ectodomain truncation of the desmosomal cadherin desmoglein 1: implications for exfoliative toxin-mediated skin blistering.
    Am J Pathol. 2010 Dec;177(6):2921-37 PMID: 21075858
  11. Desmosomal dysfunction due to mutations in desmoplakin causes arrhythmogenic right ventricular dysplasia/cardiomyopathy.
    Circ Res. 2006 Sep 15;99(6):646-55 PMID: 16917092
  12. Desmosome assembly in MDCK cells: transport of precursors to the cell surface occurs by two phases of vesicular traffic and involves major changes in centrosome and Golgi location during a Ca(2+) shift.
    Exp Cell Res. 2002 Jun 10;276(2):296-309 PMID: 12027459
  13. Cross-talk between adherens junctions and desmosomes depends on plakoglobin.
    J Cell Biol. 1997 Feb 24;136(4):919-34 PMID: 9049256
  14. Desmoplakin: an unexpected regulator of microtubule organization in the epidermis.
    J Cell Biol. 2007 Jan 15;176(2):147-54 PMID: 17227889
  15. 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
  16. Characterization of autoantibodies in pemphigus using antigen-specific enzyme-linked immunosorbent assays with baculovirus-expressed recombinant desmogleins.
    J Immunol. 1997 Aug 15;159(4):2010-7 PMID: 9257868
  17. Arrhythmogenic cardiomyopathy: etiology, diagnosis, and treatment.
    Annu Rev Med. 2010;61:233-53 PMID: 20059337
  18. Dynamics of adherens junctions in epithelial establishment, maintenance, and remodeling.
    J Cell Biol. 2011 Mar 21;192(6):907-17 PMID: 21422226
  19. The C-terminal unique region of desmoglein 2 inhibits its internalization via tail-tail interactions.
    J Cell Biol. 2012 Nov 12;199(4):699-711 PMID: 23128240
  20. Molecular organization of the desmoglein-plakoglobin complex.
    J Cell Sci. 1998 Jul 30;111 ( Pt 14):1941-9 PMID: 9645942
  21. Desmosome-ion channel interactions and their possible role in arrhythmogenic cardiomyopathy.
    Pediatr Cardiol. 2012 Aug;33(6):975-9 PMID: 22407454
  22. Exploring the Nature of Desmosomal Cadherin Associations in 3D.
    Dermatol Res Pract. 2010;2010:930401 PMID: 20672011
  23. Mutations in ATP2C1, encoding a calcium pump, cause Hailey-Hailey disease.
    Nat Genet. 2000 Jan;24(1):61-5 PMID: 10615129
  24. Roles of cadherins and catenins in cell-cell adhesion and epithelial cell polarity.
    Prog Mol Biol Transl Sci. 2013;116:3-23 PMID: 23481188
  25. Desmosomal genodermatoses.
    Br J Dermatol. 2012 Jan;166(1):36-45 PMID: 21929534
  26. Membrane-impermeable cross-linking provides evidence for homophilic, isoform-specific binding of desmosomal cadherins in epithelial cells.
    J Biol Chem. 2011 Jan 21;286(3):2143-54 PMID: 21098030
  27. Cadherin defects in inherited human diseases.
    Prog Mol Biol Transl Sci. 2013;116:361-84 PMID: 23481203
  28. Disruption of desmosome assembly by monovalent human pemphigus vulgaris monoclonal antibodies.
    J Invest Dermatol. 2009 Apr;129(4):908-18 PMID: 19037235
  29. Classical cadherins regulate desmosome formation.
    J Invest Dermatol. 2009 Aug;129(8):2072-5 PMID: 19262605
  30. Signaling dependent and independent mechanisms in pemphigus vulgaris blister formation.
    PLoS One. 2012;7(12):e50696 PMID: 23226536
  31. Loss of desmoglein 2 suggests essential functions for early embryonic development and proliferation of embryonal stem cells.
    Eur J Cell Biol. 2002 Nov;81(11):592-8 PMID: 12494996
  32. Desmoglein-1/Erbin interaction suppresses ERK activation to support epidermal differentiation.
    J Clin Invest. 2013 Apr;123(4):1556-70 PMID: 23524970
  33. Coordinated expression of desmoglein 1 and desmocollin 1 regulates intercellular adhesion.
    Differentiation. 2004 Oct;72(8):419-33 PMID: 15606501
  34. Requirement of plakophilin 2 for heart morphogenesis and cardiac junction formation.
    J Cell Biol. 2004 Oct 11;167(1):149-60 PMID: 15479741
  35. Plakophilins: Multifunctional proteins or just regulators of desmosomal adhesion?
    Biochim Biophys Acta. 2007 Jan;1773(1):69-77 PMID: 16765467
  36. E-cadherin and plakoglobin recruit plakophilin3 to the cell border to initiate desmosome assembly.
    Cell Mol Life Sci. 2011 Apr;68(8):1439-54 PMID: 20859650
  37. Dissociation of intra- and extracellular domains of desmosomal cadherins and E-cadherin in Hailey-Hailey disease and Darier's disease.
    Br J Dermatol. 2000 Apr;142(4):702-11 PMID: 10792220
  38. Interactions between ankyrin-G, Plakophilin-2, and Connexin43 at the cardiac intercalated disc.
    Circ Res. 2011 Jul 8;109(2):193-201 PMID: 21617128
  39. Delineation of diversified desmoglein distribution in stratified squamous epithelia: implications in diseases.
    Exp Dermatol. 2006 Feb;15(2):101-9 PMID: 16433681
  40. Desmoglein 2 is a receptor for adenovirus serotypes 3, 7, 11 and 14.
    Nat Med. 2011 Jan;17(1):96-104 PMID: 21151137
  41. Cell-cell connectivity: desmosomes and disease.
    J Pathol. 2012 Jan;226(2):158-71 PMID: 21989576
  42. Plakophilin 2 couples actomyosin remodeling to desmosomal plaque assembly via RhoA.
    Mol Biol Cell. 2010 Aug 15;21(16):2844-59 PMID: 20554761
  43. Plakoglobin is required for effective intermediate filament anchorage to desmosomes.
    J Invest Dermatol. 2008 Nov;128(11):2665-2675 PMID: 18496566
  44. Desmoplakin regulates desmosome hyperadhesion.
    J Invest Dermatol. 2012 Feb;132(2):482-5 PMID: 21993560
  45. The area composita of adhering junctions connecting heart muscle cells of vertebrates. II. Colocalizations of desmosomal and fascia adhaerens molecules in the intercalated disk.
    Eur J Cell Biol. 2006 Jun;85(6):469-85 PMID: 16600422
  46. Hailey-Hailey disease and tight junctions: Claudins 1 and 4 are regulated by ATP2C1 gene encoding Ca(2+) /Mn(2+) ATPase SPCA1 in cultured keratinocytes.
    Exp Dermatol. 2012 Aug;21(8):586-91 PMID: 22639968
  47. Perp is a p63-regulated gene essential for epithelial integrity.
    Cell. 2005 Mar 25;120(6):843-56 PMID: 15797384
  48. Regulation of desmocollin transcription in mouse preimplantation embryos.
    Development. 1995 Mar;121(3):743-53 PMID: 7536656
  49. Structure and function of desmosomes.
    Int Rev Cytol. 2007;264:65-163 PMID: 17964922
  50. Mutations in the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase isoform cause Darier's disease.
    J Invest Dermatol. 2003 Sep;121(3):486-9 PMID: 12925205
  51. Mechanisms of plakoglobin-dependent adhesion: desmosome-specific functions in assembly and regulation by epidermal growth factor receptor.
    J Biol Chem. 2005 Dec 2;280(48):40355-63 PMID: 16183992
  52. Pemphigus, bullous impetigo, and the staphylococcal scalded-skin syndrome.
    N Engl J Med. 2006 Oct 26;355(17):1800-10 PMID: 17065642
  53. Removal of amino-terminal extracellular domains of desmoglein 1 by staphylococcal exfoliative toxin is sufficient to initiate epidermal blister formation.
    J Dermatol Sci. 2010 Sep;59(3):184-91 PMID: 20728315
  54. Regulation of desmosome assembly and adhesion.
    Semin Cell Dev Biol. 2004 Dec;15(6):665-77 PMID: 15561586
  55. Noncentrosomal microtubules and type II myosins potentiate epidermal cell adhesion and barrier formation.
    J Cell Biol. 2012 Oct 29;199(3):513-25 PMID: 23091070
  56. Pemphigus vulgaris IgG-induced desmoglein-3 endocytosis and desmosomal disassembly are mediated by a clathrin- and dynamin-independent mechanism.
    J Biol Chem. 2008 Jun 27;283(26):18303-13 PMID: 18434319
  57. Gene replacement reveals a specific role for E-cadherin in the formation of a functional trophectoderm.
    Development. 2007 Jan;134(1):31-41 PMID: 17138661
  58. Expression of full-length desmosomol glycoproteins (desmocollins) is not sufficient to confer strong adhesion on transfected L929 cells.
    J Invest Dermatol. 1996 Apr;106(4):689-95 PMID: 8618006
  59. Cadherins and epithelial-to-mesenchymal transition.
    Prog Mol Biol Transl Sci. 2013;116:317-36 PMID: 23481201
  60. Intercellular junction assembly, dynamics, and homeostasis.
    Cold Spring Harb Perspect Biol. 2010 Feb;2(2):a000125 PMID: 20182611
  61. Desmosomes in vivo.
    Dermatol Res Pract. 2010;2010:212439 PMID: 20671997
  62. Desmosomes: interconnected calcium-dependent structures of remarkable stability with significant integral membrane protein turnover.
    J Cell Sci. 2002 Apr 15;115(Pt 8):1717-32 PMID: 11950889
  63. Sec3-containing exocyst complex is required for desmosome assembly in mammalian epithelial cells.
    Mol Biol Cell. 2010 Jan 1;21(1):152-64 PMID: 19889837
  64. Desmosomal adhesiveness is developmentally regulated in the mouse embryo and modulated during trophectoderm migration.
    Dev Biol. 2012 Sep 15;369(2):286-97 PMID: 22819675
  65. Desmosome structure, composition and function.
    Biochim Biophys Acta. 2008 Mar;1778(3):572-87 PMID: 17854763
  66. Autoantibodies against a novel epithelial cadherin in pemphigus vulgaris, a disease of cell adhesion.
    Cell. 1991 Nov 29;67(5):869-77 PMID: 1720352
  67. Keratins control intercellular adhesion involving PKC-α-mediated desmoplakin phosphorylation.
    J Cell Biol. 2013 May 27;201(5):681-92 PMID: 23690176
  68. Desmosomes: a role in cancer?
    Br J Cancer. 2007 Jun 18;96(12):1783-7 PMID: 17519903
  69. The ins and outs of E-cadherin trafficking.
    Trends Cell Biol. 2004 Aug;14(8):427-34 PMID: 15308209
  70. Tyrosine phosphorylation of plakoglobin causes contrary effects on its association with desmosomes and adherens junction components and modulates beta-catenin-mediated transcription.
    Mol Cell Biol. 2003 Oct;23(20):7391-402 PMID: 14517306
  71. Regulation of desmosome assembly in epithelial cells: kinetics of synthesis, transport, and stabilization of desmoglein I, a major protein of the membrane core domain.
    J Cell Biol. 1989 Jul;109(1):163-77 PMID: 2501314
  72. Ordered assembly of the adhesive and electrochemical connections within newly formed intercalated disks in primary cultures of adult rat cardiomyocytes.
    J Biomed Biotechnol. 2010;2010:624719 PMID: 20467587
  73. 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
  74. Adhesive and signaling functions of cadherins and catenins in vertebrate development.
    Cold Spring Harb Perspect Biol. 2009 Nov;1(5):a002949 PMID: 20066120
  75. Mutations in the plakophilin 1 gene result in ectodermal dysplasia/skin fragility syndrome.
    Nat Genet. 1997 Oct;17(2):240-4 PMID: 9326952
  76. Continual assembly of half-desmosomal structures in the absence of cell contacts and their frustrated endocytosis: a coordinated Sisyphus cycle.
    J Cell Biol. 1995 Nov;131(3):745-60 PMID: 7593194
  77. EGFR and ADAMs cooperate to regulate shedding and endocytic trafficking of the desmosomal cadherin desmoglein 2.
    Mol Biol Cell. 2009 Jan;20(1):328-37 PMID: 18987342
  78. 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
  79. Desmosomal cadherins utilize distinct kinesins for assembly into desmosomes.
    J Cell Biol. 2011 Dec 26;195(7):1185-203 PMID: 22184201
  80. Mutations in ATP2A2, encoding a Ca2+ pump, cause Darier disease.
    Nat Genet. 1999 Mar;21(3):271-7 PMID: 10080178
  81. Desmosome dynamics in migrating epithelial cells requires the actin cytoskeleton.
    Exp Cell Res. 2011 Dec 10;317(20):2814-22 PMID: 21945137
  82. Desmosomes: new perspectives on a classic.
    J Invest Dermatol. 2007 Nov;127(11):2499-515 PMID: 17934502
  83. Involvement of the ubiquitin-proteasome system in the stabilization of cell-cell contacts in human keratinocytes.
    Exp Dermatol. 2012 Oct;21(10):791-3 PMID: 22882483
  84. Low to high Ca2+ -switch causes phosphorylation and association of desmocollin 3 with plakoglobin and desmoglein 3 in cultured keratinocytes.
    Exp Dermatol. 2009 Apr;18(4):404-8 PMID: 19348003
  85. Staphylococcal exfoliative toxins: "molecular scissors" of bacteria that attack the cutaneous defense barrier in mammals.
    J Dermatol Sci. 2008 Jan;49(1):21-31 PMID: 17582744
  86. Desmosomes: adhesive strength and signalling in health and disease.
    Biochem J. 2010 Aug 1;429(3):419-33 PMID: 20626351
  87. Discriminating roles of desmosomal cadherins: beyond desmosomal adhesion.
    J Dermatol Sci. 2007 Jan;45(1):7-21 PMID: 17141479
Article Info
Journal
Trends in cell biology
Abbr.
Trends Cell Biol
ISSN
1879-3088
DOI
10.1016/j.tcb.2013.06.004
Published
2013-11-00
Epub
2013-00-24
Pages
537-46
Language
English
Region
England
NLM ID
9200566
PMCID
PMC3913269
Subset
IM
Grants
NCI NIH HHS · P30 CA060553 · United States
NIAMS NIH HHS · R01 AR041836 · United States
NCI NIH HHS · R01 CA122151 · United States
NIAMS NIH HHS · R37 AR043380 · United States
External Links
PubMed source DOI: 10.1016/j.tcb.2013.06.004 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2