ym-201636 and vicenistatin

Homotypic fusion of early endosomes is important for efficient protein trafficking and sorting. The key controller of this process is Rab5 which regulates several effectors and PtdInsPs levels, but whose mechanisms are largely unknown. Here, we report that vicenistatin, a natural product, enhanced homotypic fusion of early endosomes and induced the formation of large vacuole-like structures in mammalian cells. Unlike YM201636, another early endosome vacuolating compound, vicenistatin did not inhibit PIKfyve activity in vitro but activated Rab5-PAS pathway in cells. Furthermore, vicenistatin increased the membrane surface fluidity of cholesterol-containing liposomes in vitro, and cholesterol deprivation from the plasma membrane stimulated vicenistatin-induced vacuolation in cells. These results suggest that vicenistatin is a novel compound that induces the formation of vacuole-like structures by activating Rab5-PAS pathway and increasing membrane fluidity.

Topics: Aminoglycosides; Aminopyridines; Animals; Anti-Bacterial Agents; Cell Line; Cholesterol; Endocytosis; Endosomes; Fibroblasts; Flavoproteins; Gene Expression Regulation; HEK293 Cells; HeLa Cells; Heterocyclic Compounds, 3-Ring; Humans; Intracellular Signaling Peptides and Proteins; Lactams; Liposomes; Macrolides; Membrane Fusion; Membrane Proteins; Phosphatidylinositol 3-Kinases; Phosphatidylinositol Phosphates; Phosphoric Monoester Hydrolases; Protein Transport; rab5 GTP-Binding Proteins; Rats; Signal Transduction; Transport Vesicles; Vacuoles