| Autor: |
Resnik N; Faculty of Medicine, Institute of Cell Biology, University of Ljubljana, Vrazov trg 2, Ljubljana, Slovenia., de Luca GMR; Faculty of Science, Swammerdam Institute for Life Sciences, Leeuwenhoek Centre for Advanced Microscopy, University of Amsterdam, Amsterdam, The Netherlands., Sepčić K; Department of Biology, Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia., Romih R; Faculty of Medicine, Institute of Cell Biology, University of Ljubljana, Vrazov trg 2, Ljubljana, Slovenia., Manders E; Faculty of Science, Swammerdam Institute for Life Sciences, Leeuwenhoek Centre for Advanced Microscopy, University of Amsterdam, Amsterdam, The Netherlands., Veranič P; Faculty of Medicine, Institute of Cell Biology, University of Ljubljana, Vrazov trg 2, Ljubljana, Slovenia. peter.veranic@mf.uni-lj.si. |
| Abstrakt: |
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. |
