title: Thapsigargin distinguishes membrane fusion in the late stages of endocytosis and autophagy.
abstract: A close relationship exists between autophagy and endocytosis with both sharing lysosomes as their common end-point. Autophagy even requires a functional endocytic pathway. The point at which the two pathways merge, i.e., fusion of autophagosomes and endosomes with lysosomes is poorly understood. Early work in yeast and more recent studies in mammalian cells suggested that conventional membrane trafficking pathways control the fusion of autophagosomes with lysosomes; Rab GTPases are required to recruit tethering proteins which in turn coordinate the SNARE family of proteins that directly drive membrane fusion. Some components required for endosomes to fuse with lysosomes are also shared by autophagosomes; both are thought to require the GTPase Rab7 and the homotypic fusion and vacuole protein sorting (HOPS) complex. Essentially, the autophagosome becomes endosome-like, allowing it to recruit the common fusion machinery to deliver its contents to the lysosome. This raises an interesting question of how the cell determines when the autophagosome is ready to fuse with the endocytic system and bestows upon it the properties required to recruit the fusion machinery. Our recent work has highlighted this conundrum and shown that autophagosome fusion with lysosomes has specific distinctions from the parallel endosomal-lysosomal pathway.
authors.affiliation: MRC Protein Phosphorylation Unit, University of Dundee, Dundee, Scotland. i.ganley@dundee.ac.uk
authors.forename: Ian G
authors.initials: IG
authors.lastname: Ganley
authors.forename: Pui-Mun
authors.initials: PM
authors.lastname: Wong
authors.forename: Xuejun
authors.initials: X
authors.lastname: Jiang
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D006801:Humans; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D008561:Membrane Fusion / Q000187:drug effects*; D008954:Models, Biological; D010588:Phagosomes / Q000187:drug effects / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology*
chemical_list: D019284:Thapsigargin