Skip to main content

Advertisement

SpringerLink
Log in

Ultrastructural changes in endometrial desmosomes of desmoglein 2 mutant mice

  • Regular Article
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

The intercellular binding of desmosomal junctions is mediated by cadherins of the desmoglein (Dsg) and desmocollin (Dsc) type. Dsg2 mutant mice with deletion of a substantial segment of the extracellular EC1-EC2 domain, which is believed to participate in homo- and heterophilic desmosomal cadherin interactions, develop cardiac fibrosis and ventricular dilation. Widening of the intercellular cleft and complete intercalated disc ruptures can be observed in the hearts of these mice. Since a reduced litter size of homozygous Dsg2 mutant mice was noted and a functional correlation between desmosomes and embryo implantation has been deduced from animal studies, we looked for an alteration of desmosomes in uterine endometrial epithelium. Shape and number of desmosomes as well as the expression of Dsg2 and the desmosomal plaque protein desmoplakin (Dsp) were investigated by electron microscopy and immunohistochemistry in 12 oestrous-dated mice (7 wild type and 5 homozygous Dsg2 mutant mice) at the age of 9–17 weeks. The immunohistochemical detection of Dsg2 was diminished in the mutants and the number of desmosomes was significantly reduced as revealed by electron microscopy. In addition, the intercellular desmosomal space measured in electron micrographs was considerably widened in the Dsg2 mutants. The increased intercellular spacing can be explained by the partial deletion of the extracellular EC1–EC2 domain of Dsg2. Whether these changes explain the reduced number of offspring of homozygous Dsg2 mutant mice remains to be further investigated.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  • Al-Amoudi A, Frangakis AS (2008) Structural studies on desmosomes. Biochem Soc Trans 36:181–187

    Article  CAS  Google Scholar 

  • Al-Amoudi A, Diez DC, Betts MJ, Frangakis AS (2007) The molecular architecture of cadherins in native epidermal desmosomes. Nature 450:832–837

    Article  CAS  Google Scholar 

  • Basso C, Czarnowska E, Della Barbera M, Bauce B, Beffagna G, Wlodarska EK, Pilichou K, Ramondo A, Lorenzon A, Wozniek O, Corrado D, Daliento L, Danieli GA, Valente M, Nava A, Thiene G, Rampazzo A (2006) Ultrastructural evidence of intercalated disc remodelling in arrhythmogenic right ventricular cardiomyopathy: an electron microscopy investigation on endomyocardial biopsies. Eur Heart J 27:1847–1854

    Article  Google Scholar 

  • Boggon TJ, Murray J, Chappuis-Flament S, Wong E, Gumbiner BM, Shapiro L (2002) C-cadherin ectodomain structure and implications for cell adhesion mechanisms. Science 296:1308–1313

    Article  CAS  Google Scholar 

  • Broussard JA, Getsios S, Green KJ (2015) Desmosome regulation and signaling in disease. Cell Tissue Res 360:501–512

    Article  CAS  Google Scholar 

  • Buck VU, Windoffer R, Leube RE, Classen-Linke I (2012) Redistribution of adhering junctions in human endometrial epithelial cells during the implantation window of the menstrual cycle. Histochem Cell Biol 137:777–790

    Article  CAS  Google Scholar 

  • Buck VU, Gellersen B, Leube RE, Classen-Linke I (2015) Interaction of human trophoblast cells with gland-like endometrial spheroids: a model system for trophoblast invasion. Hum Reprod 30:906–916

    Article  CAS  Google Scholar 

  • Byers SL, Wiles MV, Dunn SL, Taft RA (2012) Mouse estrous cycle identification tool and images. PLoS One 7:e35538

    Article  CAS  Google Scholar 

  • Eshkind L, Tian Q, Schmidt A, Franke WW, Windoffer R, Leube RE (2002) Loss of desmoglein 2 suggests essential functions for early embryonic development and proliferation of embryonal stem cells. Eur J Cell Biol 81:592–598

    Article  CAS  Google Scholar 

  • Farquhar MG, Palade GE (1963) Junctional complexes in various epithelia. J Cell Biol 17:375–412

    Article  CAS  Google Scholar 

  • Fujiwara M, Nagatomo A, Tsuda M, Obata S, Sakuma T, Yamamoto T, Suzuki ST (2015) Desmocollin-2 alone forms functional desmosomal plaques, with the plaque formation requiring the juxtamembrane region and plakophilins. J Biochem 158:339–353

    Article  CAS  Google Scholar 

  • Garrod D, Chidgey M (2008) Desmosome structure, composition and function. Biochim Biophys Acta 1778:572–587

    Article  CAS  Google Scholar 

  • Holthofer B (2007) Konditionale Mutagenese von Desmoglein 2 in der Maus. Institute of Anatomy, Johannes Gutenberg-University, Mainz. Dissertation, pp 1–208. https://publications.ub.uni-mainz.de/theses/frontdoor.php?source_opus=1540

  • Holthofer B, Windoffer R, Troyanovsky S, Leube RE (2007) Structure and function of desmosomes. Int Rev Cytol 264:65–163

    Article  Google Scholar 

  • Illingworth IM, Kiszka I, Bagley S, Ireland GW, Garrod DR, Kimber SJ (2000) Desmosomes are reduced in the mouse uterine luminal epithelium during the preimplantation period of pregnancy: a mechanism for facilitation of implantation. Biol Reprod 63:1764–1773

    Article  CAS  Google Scholar 

  • Kamekura R, Kolegraff KN, Nava P, Hilgarth RS, Feng M, Parkos CA, Nusrat A (2014) Loss of the desmosomal cadherin desmoglein-2 suppresses colon cancer cell proliferation through EGFR signaling. Oncogene 33:4531–4536

    Article  CAS  Google Scholar 

  • Kant S, Krull P, Eisner S, Leube RE, Krusche CA (2012) Histological and ultrastructural abnormalities in murine desmoglein 2-mutant hearts. Cell Tissue Res 348:249–259

    Article  CAS  Google Scholar 

  • Koch PJ, Walsh MJ, Schmelz M, Goldschmidt MD, Zimbelmann R, Franke WW (1990) Identification of desmoglein, a constitutive desmosomal glycoprotein, as a member of the cadherin family of cell adhesion molecules. Eur J Cell Biol 53:1–12

    CAS  PubMed  Google Scholar 

  • Koch PJ, Goldschmidt MD, Walsh MJ, Zimbelmann R, Franke WW (1991) Complete amino acid sequence of the epidermal desmoglein precursor polypeptide and identification of a second type of desmoglein gene. Eur J Cell Biol 55:200–208

    CAS  PubMed  Google Scholar 

  • Kowalczyk AP, Green KJ (2013) Structure, function, and regulation of desmosomes. Prog Mol Biol Transl Sci 116:95–118

    Article  CAS  Google Scholar 

  • Krusche CA, Holthofer B, Hofe V, van de Sandt AM, Eshkind L, Bockamp E, Merx MW, Kant S, Windoffer R, Leube RE (2011) Desmoglein 2 mutant mice develop cardiac fibrosis and dilation. Basic Res Cardiol 106:617–633

    Article  CAS  Google Scholar 

  • Lowndes M, Rakshit S, Shafraz O, Borghi N, Harmon RM, Green KJ, Sivasankar S, Nelson WJ (2014) Different roles of cadherins in the assembly and structural integrity of the desmosome complex. J Cell Sci 127:2339–2350

    Article  CAS  Google Scholar 

  • McDowell EM, Trump BF (1976) Histologic fixatives suitable for diagnostic light and electron microscopy. Arch Pathol Lab Med 100:405–414

    CAS  PubMed  Google Scholar 

  • Nava P, Laukoetter MG, Hopkins AM, Laur O, Gerner-Smidt K, Green KJ, Parkos CA, Nusrat A (2007) Desmoglein-2: a novel regulator of apoptosis in the intestinal epithelium. Mol Biol Cell 18:4565–4578

    Article  CAS  Google Scholar 

  • North AJ, Bardsley WG, Hyam J, Bornslaeger EA, Cordingley HC, Trinnaman B, Hatzfeld M, Green KJ, Magee AI, Garrod DR (1999) Molecular map of the desmosomal plaque. J Cell Sci 112(Pt 23):4325–4336

    CAS  PubMed  Google Scholar 

  • Pilichou K, Nava A, Basso C, Beffagna G, Bauce B, Lorenzon A, Frigo G, Vettori A, Valente M, Towbin J, Thiene G, Danieli GA, Rampazzo A (2006) Mutations in desmoglein-2 gene are associated with arrhythmogenic right ventricular cardiomyopathy. Circulation 113:1171–1179

    Article  CAS  Google Scholar 

  • Preston AM, Lindsay LA, Murphy CR (2004) Progesterone treatment and the progress of early pregnancy reduce desmoglein 1&2 staining along the lateral plasma membrane in rat uterine epithelial cells. Acta Histochem 106:345–351

    Article  CAS  Google Scholar 

  • Preston AM, Lindsay LA, Murphy CR (2006) Desmosomes in uterine epithelial cells decrease at the time of implantation: an ultrastructural and morphometric study. J Morphol 267:103–108

    Article  Google Scholar 

  • Reynolds ES (1963) The use of lead citrate at high pH as an electron-opaque stain in electron microscopy. J Cell Biol 17:208–212

    Article  CAS  Google Scholar 

  • Rugh R (1968) The mouse; its reproduction and development. Oxford University Press, New York

    Google Scholar 

  • Schafer S, Koch PJ, Franke WW (1994) Identification of the ubiquitous human desmoglein, Dsg2, and the expression catalogue of the desmoglein subfamily of desmosomal cadherins. Exp Cell Res 211:391–399

    Article  CAS  Google Scholar 

  • Schafer S, Stumpp S, Franke WW (1996) Immunological identification and characterization of the desmosomal cadherin Dsg2 in coupled and uncoupled epithelial cells and in human tissues. Differentiation 60:99–108

    Article  CAS  Google Scholar 

  • Schlegel N, Meir M, Heupel WM, Holthofer B, Leube RE, Waschke J (2010) Desmoglein 2-mediated adhesion is required for intestinal epithelial barrier integrity. Am J Physiol Gastrointest Liver Physiol 298:G774–G783

    Article  CAS  Google Scholar 

  • Spindler V, Meir M, Vigh B, Flemming S, Hutz K, Germer CT, Waschke J, Schlegel N (2015) Loss of Desmoglein 2 contributes to the pathogenesis of Crohn's disease. Inflamm Bowel Dis 21:2349–2359

    PubMed  Google Scholar 

  • Thomason HA, Scothern A, McHarg S, Garrod DR (2010) Desmosomes: adhesive strength and signalling in health and disease. Biochem J 429:419–433

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Molecular and Cellular Anatomy, RWTH Aachen University, Wendlingweg 2, 52074, Aachen, Germany

    Volker U. Buck, Matthias Hodecker, Sabine Eisner, Rudolf E. Leube, Claudia A. Krusche & Irmgard Classen-Linke

Authors
  1. Volker U. Buck
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Matthias Hodecker
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sabine Eisner
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rudolf E. Leube
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Claudia A. Krusche
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Irmgard Classen-Linke
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Irmgard Classen-Linke.

Ethics declarations

Ethical approval

All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted. This article does not contain any studies with human participants performed by any of the authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Buck, V.U., Hodecker, M., Eisner, S. et al. Ultrastructural changes in endometrial desmosomes of desmoglein 2 mutant mice. Cell Tissue Res 374, 317–327 (2018). https://doi.org/10.1007/s00441-018-2869-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-018-2869-z

Keywords

Search

Navigation