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Histochemistry and Cell Biology

, Volume 152, Issue 3, pp 195–206 | Cite as

Depletion of the cellular cholesterol content reduces the dynamics of desmosomal cadherins and interferes with desmosomal strength

  • Nataša Resnik
  • Giulia Maria Rita de Luca
  • Kristina Sepčić
  • Rok Romih
  • Erik Manders
  • Peter VeraničEmail author
Original Paper

Abstract

Desmosomal cadherins, desmocollins, and desmogleins are cholesterol-dependent entities responsible for the stable adhesion of desmosomes in epithelial cells. Here, we investigated the influence of cellular cholesterol depletion on the dynamic properties of the desmosomal cadherin desmocollin, particularly the lateral mobility and distribution of desmocollin 2 (Dsc2-YFP) in the plasma membrane, and how these properties influence the adhesion strength of desmosomes. Depletion of cellular cholesterol decreased the lateral mobility of Dsc2-YFP and caused dispersion of Dsc2-YFP in the plasma membrane of epithelial MDCK cells. As a consequence of the altered Dsc2-YFP dynamics, the adhesive strength of desmosomes was weakened. Moreover, our study is the first to show and quantify the co-association of desmosomes with cholesterol/sphingomyelin-enriched membrane domains at the ultrastructural level. Taken together, our data emphasize a critical role for the cellular cholesterol content in regulating the lateral mobility and distribution of Dsc2 and show that cholesterol depletion reduces the strength of desmosomal adhesions.

Keywords

Cholesterol Desmosomes Desmosomal cadherins Lateral mobility Cholesterol/sphingomyelin-enriched membrane domains 

Abbreviations

BSA

Bovine serum albumin

D

Diffusion coefficient

Dsc2-YFP

Desmocollin 2 tagged with yellow fluorescent protein

FRAP

Fluorescence recovery after photobleaching

MCD

Methyl-β-cyclodextrin

M

Mobile fraction

OlyA/PlyB

Ostreolysin A/pleurotolysin B

PBS

Phosphate-buffered saline

Notes

Acknowledgements

The study was supported by Slovenian Research Agency (ARRS) grants P3-0108, P1-0207 and J3-7494 and MRIC UL IP-0510 Infrastructure program. MDCK cells with Dsc2-YFP expression were kindly provided by Prof. Rudolf Leube (University Hospital RWTH Aachen, Germany). We express gratitude to Ronald Breedijk, Sabina Železnik, Sanja Čabraja, Linda Štrus, and Nada Pavlica Dubarič for their technical assistance.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

418_2019_1797_MOESM1_ESM.docx (225 kb)
Supplementary material 1 (DOCX 224 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Nataša Resnik
    • 1
  • Giulia Maria Rita de Luca
    • 2
  • Kristina Sepčić
    • 3
  • Rok Romih
    • 1
  • Erik Manders
    • 2
  • Peter Veranič
    • 1
    Email author
  1. 1.Faculty of Medicine, Institute of Cell BiologyUniversity of LjubljanaLjubljanaSlovenia
  2. 2.Faculty of Science, Swammerdam Institute for Life Sciences, Leeuwenhoek Centre for Advanced MicroscopyUniversity of AmsterdamAmsterdamThe Netherlands
  3. 3.Department of Biology, Biotechnical FacultyUniversity of LjubljanaLjubljanaSlovenia

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