Presenilin-1 inhibits δ-catenin-induced cellular branching and promotes δ-catenin processing and turnover

Although δ-catenin/neural plakophilin-related armadillo protein (NPRAP) was reported to interact with presenilin-1 (PS-1), the effects of PS-1 on δ-catenin have not been established. In this study, we report that overexpression of PS-1 inhibits the δ-catenin-induced dendrite-like morphological changes in NIH 3T3 cells and promotes δ-catenin processing and turnover. The effects of PS-1 on endogenous δ-catenin processing were confirmed in hippocampal neurons overexpressing PS-1, as well as in the transgenic mice expressing the disease-causing mutant PS-1 (M146V). In addition, disease-causing mutant PS-1 (M146V and L286V) enhanced δ-catenin processing, whereas PS-1/γ-secretase inhibitors could block the formation of processed forms of δ-catenin. Together, our findings suggest that PS-1 can affect δ-catenin-induced morphogenesis possibly through the regulation of its processing and stability.