title: ATG16L1 meets ATG9 in recycling endosomes: additional roles for the plasma membrane and endocytosis in autophagosome biogenesis.
abstract: Autophagosomes are formed by double-membraned structures, which engulf portions of cytoplasm. Autophagosomes ultimately fuse with lysosomes, where their contents are degraded. The origin of the autophagosome membrane may involve different sources, such as mitochondria, Golgi, endoplasmic reticulum, plasma membrane, and recycling endosomes. We recently observed that ATG9 localizes on the plasma membrane in clathrin-coated structures and is internalized following a classical endocytic pathway through early and then recycling endosomes. By contrast, ATG16L1 is also internalized by clathrin-mediated endocytosis but via different clathrin-coated pits, and appears to follow a different route to the recycling endosomes. The R-SNARE VAMP3 mediates the coalescence of the 2 different pools of vesicles (containing ATG16L1 or ATG9) in recycling endosomes. The heterotypic fusion between ATG16L1- and ATG9-containing vesicles strongly correlates with subsequent autophagosome formation. Thus, ATG9 and ATG16L1 both traffic from the plasma membrane to autophagic precursor structures and provide 2 routes from the plasma membrane to autophagosomes.
authors.affiliation: Department of Medical Genetics; Cambridge Institute for Medical Research; University of Cambridge; Cambridge UK.
authors.forename: Claudia
authors.initials: C
authors.lastname: Puri
authors.affiliation: Department of Medical Genetics; Cambridge Institute for Medical Research; University of Cambridge; Cambridge UK.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Renna
authors.affiliation: Department of Medical Genetics; Cambridge Institute for Medical Research; University of Cambridge; Cambridge UK.
authors.forename: Carla Figueira
authors.initials: CF
authors.lastname: Bento
authors.affiliation: Department of Medical Genetics; Cambridge Institute for Medical Research; University of Cambridge; Cambridge UK.
authors.forename: Kevin
authors.initials: K
authors.lastname: Moreau
authors.affiliation: Department of Medical Genetics; Cambridge Institute for Medical Research; University of Cambridge; Cambridge UK.
authors.forename: David C
authors.initials: DC
authors.lastname: Rubinsztein
mesh_terms: D000818:Animals; D001343:Autophagy; D002352:Carrier Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D008954:Models, Biological; D010588:Phagosomes / Q000378:metabolism*; D021381:Protein Transport
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins
keywords: ATG16L1; VAMP3; autophagy; endocytosis; mATG9; recycling endosome