Autophagosome formation from membrane compartments enriched in phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic reticulum.
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.
Axe
Elizabeth L
EL
Signalling Programme, Babraham Institute, Babraham, Cambridge, England, UK.
Walker
Simon A
SA
Manifava
Maria
M
Chandra
Priya
P
Roderick
H Llewelyn
HL
Habermann
Anja
A
Griffiths
Gareth
G
Ktistakis
Nicholas T
NT
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
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