(A) Model pathway for autophagosome formation. Sites of action for
CQ, Wortmannin (wort), rapamycin (Rap), and lithium chloride (LiCl) are shown.
(B) Impact of LiCl on steady-levels of indicated disease
proteins as determined by western blot. Cells were treated with for 18 hr prior
to lysis of Cos-7 cells. C-E show fluorescence micrographs of Cos-7 cells
treated as indicated. (C) The impact of Wort and CQ on the
accumulation of E90K in puncta. (D) The impact of siRNA KD of ATG5
on the accumulation of E90K in puncta. One hundred cells per slide were scored
for the presence of puncta and cells that contained >10 puncta were
judged as punctate. Data are represented as mean +/−SEM. Asterisks (*)
indicates a p<0.05 in a t-test ; n=3. (E) Localization of
E90K in relation to autophagic markers. Cells immunostained for LAMP-2 (lysosome
marker), or p62 (autophagy marker) are shown. Additionally, cells co-expressing
E90K and ATZ were immunostained with α1AT. Insets show colocalization of
LAMP-2 and p62 with E90K puncta. (F) Immunogold transmission
electron microscopy (TEM) of Cos-7 cells expressing E90K GnRHR-GFP. Immunogold
staining was performed against the GFP tag and gold particles are indicated with
arrows. Mitochondria (M), endoplasmic reticulum (ER), nuclei (N), and autophagic
vesicles (AV) are labeled. Scale bar = 1 μM. See also Figures S2 and S3.