Figure 8.

Schematic illustration of Vps34 deficiency in podocytes. (A) Vps34 deficiency leads to incomplete formation of the autophagosomal membrane, resulting in deficient autophagy and autophagosomal fusion. LC3 can still be converted from LC3-I to -II, but no functional autophagosome is formed. It leads to an accumulation of nondegraded LC3 and p62 as well as an accumulation of vacant lysosomes and accumulation of Lamp1/2. The absence of PI(3)P causes a blockade in autophagosomal formation and autophagosomal–lysosomal fusion. (B) Endosomal trafficking is blocked in Vps34-deficient podocytes. Lack of PI(3)P production inhibits fluid-phase uptake, receptor-mediated endocytosis, and maturation of the early endosome to the late endosome, resulting in an accumulation of Rab5. Rab7, a marker for the late endosome, is not affected. Lamp1/2, markers for the lysosome, are upregulated, indicating unused lysosomes because of insufficient endolysosomal fusion.