title: Phosphatidylinositol-3-phosphate clearance plays a key role in autophagosome completion.
abstract: BACKGROUND
  The biogenesis of autophagosomes, the hallmark of autophagy, depends on the function of the autophagy-related (Atg) proteins and the generation of phosphatidylinositol-3-phosphate (PtdIns3P) at the phagophore assembly site (PAS), the location where autophagosomes arise. The current model is that PtdIns3P is involved primarily in the recruitment of Atg proteins to the PAS and that once an autophagosome is complete, the Atg machinery is released from its surface back into the cytoplasm and reused for the formation of new vesicles.
  
  
  RESULTS
  We have identified a PtdIns3P phosphatase, Ymr1, that is essential for the normal progression of both bulk and selective types of autophagy. This protein is recruited to the PAS at an early stage of formation of this structure through a process that requires both its GRAM domain and its catalytic activity. In the absence of Ymr1, Atg proteins fail to dissociate from the limiting membrane of autophagosomes, and these vesicles accumulate in the cytoplasm.
  
  
  CONCLUSIONS
  Our data thus reveal a key role for PtdIns3P turnover in the regulation of the late steps of autophagosome biogenesis and indicate that the disassembly of the Atg machinery from the surface of autophagosomes is a requisite for their fusion with the vacuole.
authors: Department of Cell Biology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
authors: Eduardo
authors: E
authors: Cebollero
authors: Aniek
authors: A
authors: van der Vaart
authors: Mantong
authors: M
authors: Zhao
authors: Ester
authors: E
authors: Rieter
authors: Daniel J
authors: DJ
authors: Klionsky
authors: J Bernd
authors: JB
authors: Helms
authors: Fulvio
authors: F
authors: Reggiori
mesh_terms: D001343:Autophagy / Q000502:physiology*; D005656:Fungal Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D015003:Yeasts / Q000166:cytology* / Q000235:genetics / Q000378:metabolism
chemical_list: D005656:Fungal Proteins; D018129:Phosphatidylinositol Phosphates; C055525:phosphatidylinositol 3-phosphate