Depletion of the cellular cholesterol content reduces the dynamics of desmosomal cadherins and interferes with desmosomal strength
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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.
KeywordsCholesterol Desmosomes Desmosomal cadherins Lateral mobility Cholesterol/sphingomyelin-enriched membrane domains
Bovine serum albumin
Desmocollin 2 tagged with yellow fluorescent protein
Fluorescence recovery after photobleaching
Ostreolysin A/pleurotolysin B
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.
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