Extracellularly truncated desmoglein 1 compromises desmosomes in MDCK cells

The formation and stability of epithelial tissue involves cell adhesion and the connection of the intermediate filaments of contiguous cells, mediated by desmosomes. The cadherin family members Desmocollins (Dsc) and Desmogle ins (Dsg) mediate desmosome extracellular adhesion. The main intracellular molecules identified linking Dscs and Dsgs with the intermediate filament n etwork are Plakoglobin (PG), Plakophilins (PPs) and Desmoplakin (DP). Previ ous studies on desmosome-mediated adhesion have focused on the intracellula r domains of Dsc and Dsg because of their capacity to interact with PG, PPs and DP. This study examines the role of the extracellular domain of Dsg1 u pon desmosome stability in MDCK cells. Dsg1 was constructed containing an e xtracellular deletion (Dsg Delta 1EC) and was expressed in MDCK cells. A hi gh expressor Dsg Delta 1EC/MDCK clone was obtained and analysed for its cap acity to form desmosomes in cell monolayers and when growing under mechanic al stress in three-dimensional collagen cultures. Phenotypic changes associ ated with the ectopic expression of Dsg1 Delta EC in MDCK cells were: distu rbance of the cytokeratin network, a change in the quality and number of de smosomes and impairment of the formation of cysts in suspension cultures. I nterestingly, Dsg1DEC was not localized in desmosomes, but was still able t o maintain its intracytoplasmic interaction with PG, suggesting that the di sruptive effects were largely due to PG and/or PP sequestration.