title: Autophagosome formation from membrane compartments enriched in phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic reticulum.
abstract: Autophagy is the engulfment of cytosol and organelles by double-membrane vesicles termed autophagosomes. Autophagosome formation is known to require phosphatidylinositol 3-phosphate (PI(3)P) and occurs near the endoplasmic reticulum (ER), but the exact mechanisms are unknown. We show that double FYVE domain-containing protein 1, a PI(3)P-binding protein with unusual localization on ER and Golgi membranes, translocates in response to amino acid starvation to a punctate compartment partially colocalized with autophagosomal proteins. Translocation is dependent on Vps34 and beclin function. Other PI(3)P-binding probes targeted to the ER show the same starvation-induced translocation that is dependent on PI(3)P formation and recognition. Live imaging experiments show that this punctate compartment forms near Vps34-containing vesicles, is in dynamic equilibrium with the ER, and provides a membrane platform for accumulation of autophagosomal proteins, expansion of autophagosomal membranes, and emergence of fully formed autophagosomes. This PI(3)P-enriched compartment may be involved in autophagosome biogenesis. Its dynamic relationship with the ER is consistent with the idea that the ER may provide important components for autophagosome formation.
authors: Signalling Programme, Babraham Institute, Babraham, Cambridge, England, UK.
authors: Elizabeth L
authors: EL
authors: Axe
authors: Simon A
authors: SA
authors: Walker
authors: Maria
authors: M
authors: Manifava
authors: Priya
authors: P
authors: Chandra
authors: H Llewelyn
authors: HL
authors: Roderick
authors: Anja
authors: A
authors: Habermann
authors: Gareth
authors: G
authors: Griffiths
authors: Nicholas T
authors: NT
authors: Ktistakis
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids; D000818:Animals; D001343:Autophagy; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D002451:Cell Compartmentation; D002460:Cell Line; D002470:Cell Survival; D002999:Clone Cells; D015536:Down-Regulation; D004721:Endoplasmic Reticulum / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism* / Q000648:ultrastructure; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D010588:Phagosomes / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism
chemical_list: D000596:Amino Acids; D002352:Carrier Proteins; D008869:Microtubule-Associated Proteins; D018129:Phosphatidylinositol Phosphates; D011993:Recombinant Fusion Proteins; C426003:ZFYVE1 protein, human; C055525:phosphatidylinositol 3-phosphate; D049452:Green Fluorescent Proteins; D019869:Phosphatidylinositol 3-Kinases