PRESENILIN-1 INTERACTION IN THE BRAIN WITH A NOVEL MEMBER OF THE ARMADILLO FAMILY

One approach to understanding the function of presenilin 1 (PS1), is t o discover those proteins with which it interacts. Evidence for a func tion in developmental patterning came from C. elegans, in which a PS h omologue was identified by screening for suppressors of a mutation in Notch/lin-12, a gene which specifies cell fate. However, this genetic experiment cannot determine which proteins directly interact with PS1. Therefore, we utilized the two hybrid system and confirmatory co-immu noprecipitations to identify a novel catenin, termed gamma-catenin, wh ich interacts with PS1 and is principally expressed in brain. The cate nins are a gene family related to the Armadillo gene in Drosophila, so me of which appear to have dual roles - they are components of cell-ce ll adherens junctions, and may serve as intermediates in the Wingless (Wg) signaling pathway, which, like Notch/lin-12, is also responsible for a variety of inductive signaling events. In the non-neuronal 293 c ell line, PS1 interacted with gamma-catenin, the family member with th e greatest homology to Armadillo. Wg and Notch interactions are mediat ed by the Dishevelled gene, which may form a signaling complex with PS 1 and Wg pathway intermediates to regulate the function of the Notch/ lin-12 gene.