Endoproteolysis, Aβ, and NICD production by F411Y/S438P mutant in
mouse embryonic fibroblasts. A, PS double knock-out cells were
transiently transfected with C1–99pcDNA, PS1pcDNA3.1/Zeo, or
F411Y/S438PpcDNA3. 1/Zeo, and siRNA for NCT or control siRNA (cont.
siRNA), as indicated. Cells were recovered and analyzed by immunoblotting
with specific antibodies. The endoproteolysis of PS1 was detected by the
production of PS1 CTF. B, NCT knock-out (KO) cells or wild
type (WT) fibroblast cells were transiently transfected with
C1–99pcDNA, PS1pcDNA3.1/Zeo, or F411Y/S438PpcDNA3.1/Zeo as indicated.
Cells and media were recovered and analyzed by immunoblotting with specific
antibodies (human PS1-specific antibody (PS1L) was used for PS1). Aβ was
detected in media. Synthetic Aβ40 (30 pg) was loaded as indicated.
C, NCT knock-out cells (KO) or wild type (WT)
fibroblast cells were transiently transfected with
pCS2+mNΔEmyc, PS1pcDNA3.1/Zeo, or F411Y/S438PpcDNA3.1/Zeo as
indicated. Membrane-bound mNotch-1 (NΔE) was expressed from
the pCS2+mNΔEmyc vector. 48 h after transfection, cells were
incubated with 10 μm lactacystin for 4 h, recovered, and
analyzed by immunoblotting with specific antibodies. The asterisks
indicate nonspecific bands.