Dimerization of presenilin-1 in vivo: suggestion of novel regulatory mechanisms leading to higher order complexes

• Published in: Biochemical and biophysical research communications 2003-01, Vol.301 (1), p.119-126
• Main Authors: Hébert, Sébastien S, Godin, Chantal, Tomiyama, Takami, Mori, Hiroshi, Lévesque, Georges
• Format: Article
• Language: English
• Subjects: Animals; Cell Line; Dimerization; Humans; Macromolecular Substances; Membrane Proteins - chemistry; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Molecular Weight; Mutation; Oligomerization; Presenilin; Presenilin-1; Protein dimerization; Protein Structure, Quaternary; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Two-Hybrid System Techniques; Western blotting; Yeast two-hybrid; γ-Secretase
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/S0006-291X(02)02984-4

A growing body of evidence indicates that presenilins could exist and be active as oligomeric complexes. Using yeast two-hybrid and cell culture analysis, we provide evidence that presenilin-1 (PS1) may self-oligomerize giving rise to specific full-length/full-length homodimers. When expressed in N2A and HEK239T cultured cells, full-length PS1-wt and 5 ′myc-PS1-wt form specific homodimers corresponding to twice their molecular weight. The Alzheimer’s disease-associated PS1 mutations Y115H, M146L, L392V, ΔE10(PS1 1–289/320–467), the γ-secretase dominant negative mutant D257A, and the PS1 polymorphism mutant E318G do not affect their ability to self-oligomerize. Under non-denaturing conditions, endogenous PS1 forms specific homo-oligomers in human cultured cells. The results obtained herein suggest that PS1 associates intramolecularly to form higher order complexes, which may be needed for endoproteolytic cleavage and/or γ-secretase-associated activity.