Presenilin affects arm/beta-catenin localization and function in Drosophila

Presenilin is an essential gene for development that when disrupted leads t o a neurogenic phenotype that closely resembles Notch loss of function in D rosophila. In humans, many naturally occurring mutations in Presenilin 1 or 2 cause early onset Alzheimer's disease. Both loss of expression and overe xpression of Presenilin suggested a role for this protein in the localizati on of Armadillo/beta -catenin. In blastoderm stage Presenilin mutants, Arm is aberrantly distributed, often in Ubiquitin-immunoreactive cytoplasmic in clusions predominantly located basally in the cell. These inclusions were n ot observed in loss of function Notch mutants, suggesting that failure to p rocess Notch is not the only consequence of the loss of Presenilin function . Human presenilin 1 expressed in Drosophila produces embryonic phenotypes resembling those associated with mutations in Armadillo and exhibited reduc ed Armadillo at the plasma membrane that is likely due to retention of Arma dillo in a complex with Presenilin. The interaction between Armadillo/beta -catenin and Presenilin 1 requires a third protein which may be delta -cate nin. Our results suggest that Presenilin may regulate the delivery of a mul tiprotein complex that regulates Armadillo trafficking between the adherens junction and;he proteasome. (C) 2000 Academic Press.