Tyr682 in the Intracellular Domain of APP Regulates Amyloidogenic APP Processing In Vivo
Figure 3
Normal expression of the mutant APP allele.
A, The genetic manipulation of the APP gene locus in APPYG/YG mice does not affect transcription/splicing of APP since mRNA APP levels are comparable to those transcribed in age-matched APPWT/WT mice (analogous data were obtained using Beta Actin as housekeeping gene). B, APP and APP-derived CTFs are processed by the lysosomes. Inhibition of lysosomal activity by chloroquine (Chl.) results in accumulation of APP and APP derived fragments. The asterisks indicate APP-CTFs that are derived by cleavages in the ectodomain NH2-terminal to the site processed by BACE1. The effectiveness of Chl. in inhibiting lysosomal degradation (inhibition occurs at 50 µM concentration but not at 5 mM) is confirmed by the accumulation on LC3II [78]. The antibody against LC3 is from Cell Signaling.