A nuclear function for the presenilin 1 neuronal partner NPRAP/δ-catenin.

Presenilin-1 (PS1) is a broadly expressed transmembrane protein that is often mutated in familial Alzheimer's disease (AD). In addition to its role in amyloid production, PS1 interacts with several protein partners, including the neural plakophilin-related armadillo protein (NPRAP or δ-catenin). Although studies have suggested that NPRAP affects cell adhesion, other data suggest that it can modulate gene expression. To investigate the transcriptional effects of NPRAP, we over-expressed NPRAP and measured gene expression using a microarray. We found that multiple genes, including BCHE, which has been linked to AD, were regulated by NPRAP. Furthermore, we showed that NPRAP nuclear translocation was required for gene regulation. Our results implicate NPRAP as a brain-specific signaling molecule with distinct roles at the cell junction and the nucleus.