The role of Alzheimer's disease-related presenilin 1 in intercellular adhesion

Citation
N. Singh et al., The role of Alzheimer's disease-related presenilin 1 in intercellular adhesion, EXP CELL RE, 263(1), 2001, pp. 1-13
Citations number
87
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
EXPERIMENTAL CELL RESEARCH
ISSN journal
0014-4827 → ACNP
Volume
263
Issue
1
Year of publication
2001
Pages
1 - 13
Database
ISI
SICI code
0014-4827(20010201)263:1<1:TROADP>2.0.ZU;2-I
Abstract
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.