A myristoylated calcium-binding protein that preferentially interacts withthe Alzheimer's disease presenilin 2 protein

It is well established that mutations in the presenilin 1 and 2 genes cause the majority of early onset Alzheimer's disease (AD). However, our underst anding of the cellular functions of the proteins they encode remains rudime ntary. Knowledge of proteins with which the prescnilins interact should lea d to a better understanding of presenilin function in normal and disease st ates. We report here the identification of a calcium-binding protein, calmy rin, that interacts preferentially with presenilin 2 (PS2). Calmyrin is myr istoylated, membrane-associated, and colocalizes with PS2 when the two prot eins are overexpressed in HeLa cells, Yeast two-hybrid liquid assays, affin ity chromatography, and coimmunoprecipitation experiments confirm binding b etween PS2 and calmyrin. Functionally, calmyrin and PS2 increase cell death when cotransfected into HeLa cells. These results allude to several provoc ative possibilities for a dynamic role of calmyrin in signaling, cell death , and AD.