Most cases of familial early-onset Alzheimer's disease are caused by mutati
ons in the presenilin 1 (PS1) gene. However, the cellular functions of PS1
are unknown. We showed predominant localization of PS1 to cell-cell contact
s of the plasma membrane in human prostate epithelial tissue and in a human
epithelial cell fine HEp2 stably transfected with an inducible PS1 constru
ct, PS1 co-immunoprecipitated with beta -catenin from cell lysates of stabl
e transfectants, Conversely, PS1 lacking the PS1-beta -catenin interaction
site did not co-immunoprecipitate with beta -catenin and was not recruited
to the cell-cell contacts. L cells, which do not form tight intercellular c
ontacts, formed clusters of adhered cells after stable transfection with GF
P-PS1 cDNA and demonstrated a clear preference for independent aggregation
in the mixed cultures. However, L cells transfected with mutant GFP-PS1 con
structs, which had a truncated N-terminus of PS1 or deleted PS1-beta -caten
in interaction site, failed to form intercellular contacts. In addition, in
primary cultures of mouse cortical neurons PS1 was highly concentrated on
the surface of extended growth cones. Taken together, our results suggest a
n important role of PS1 in intercellular adhesion in epithelial cells and n
eurons. (C) 2001 Academic Press.