Extracellularly truncated desmoglein 1 compromises desmosomes in MDCK cells.

Summary The formation and stability of epithelial tissue involves cell adhesion and the connection of the intermediate filaments of contiguous cells, mediatedby desmosomes.Thecadherinfamily members Desmocollins (Dsc) and Desmogleins (Dsg) mediate desmosome extracellular adhesion. The main intracellular molecules identifiedlinking Dscs andDsgs with theintermediate filament network are Plakoglobin (PG), Plakophilins (PPs) and Desmoplakin (DP). Previous studies on desmosome-mediated adhesion have focused on the intracellular domains of Dsc and Dsg because of their capacity to interact with PG, PPs and DP. This study examines the roleofthe extracellular domain ofDsg1 upon desmosomestability in MDCK cells. Dsg1 was constructed containing an extracellular deletion (DsgD 1EC) and was expressed in MDCK cells. A high expressor DsgD 1EC/MDCK clone was obtained and analysed forits capacity to formdesmosomes incell monolayers andwhengrowingundermechanicalstress in three-dimensional collagen cultures. Phenotypic changes associated with the ectopic expression of Dsg1D EC in MDCK cells were: disturbance of the cytokeratin network, a change in the quality and number of desmosomes and impairment of the formation of cysts in suspension cultures. Interestingly, Dsg1D EC was not localized in desmosomes, but was still able to maintain its intracytoplasmic interaction with PG, suggesting that the disruptive effects were largely due to PG and/or PP sequestration.