title: The plasma membrane as a control center for autophagy.
abstract: Autophagosomes may derive membrane from diverse sources, including the plasma membrane, Golgi, endoplasmic reticulum and mitochondria. The plasma membrane contributes membrane to ATG12-ATG5-ATG16L1-positive phagophore precursor vesicles (LC3-negative) by both clathrin-dependent and -independent routes. We recently observed that ARF6 regulates autophagy and that this could be explained, at least in part, by its role in the generation of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P 2], which influences endocytic uptake of plasma membrane into autophagosome precursors. The subsequent maturation of these small phagophore precursors into phagophores (ATG12-ATG5-ATG16L1-positive and LC3-positive), is assisted by SNARE-mediated homotypic fusion that increase their size and enhance their ability to acquire LC3-II. It appears that a plasma membrane-derived pool of VAMP7 is a key mediator of these fusion events. Thus, events at the plasma membrane may regulate distinct steps in the biogenesis of phagophores.
authors.affiliation: Department of Medical Genetics, Cambridge Institute for Medical Research, Wellcome/MRC Building, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Kevin
authors.initials: K
authors.lastname: Moreau
authors.forename: David C
authors.initials: DC
authors.lastname: Rubinsztein
mesh_terms: D001343:Autophagy; D002462:Cell Membrane / Q000378:metabolism*; D004705:Endocytosis; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D008954:Models, Biological; D050683:R-SNARE Proteins / Q000378:metabolism
chemical_list: D050683:R-SNARE Proteins