The Atg1-Atg13 complex regulates Atg9 and Atg23 retrieval transport from the pre-autophagosomal structure

Dev Cell. 2004 Jan;6(1):79-90. doi: 10.1016/s1534-5807(03)00402-7.

Abstract

To survive extreme environmental conditions, and in response to certain developmental and pathological situations, eukaryotic organisms employ the catabolic process of autophagy. Structures targeted for destruction are enwrapped by double-membrane vesicles, then delivered into the interior of the lysosome/vacuole. Despite the identification of many specific components, the molecular mechanism that directs formation of the sequestering vesicles remains largely unknown. We analyzed the trafficking of Atg23 and the integral membrane protein Atg9 in the yeast Saccharomyces cerevisiae. These components localize both to the pre-autophagosomal structure (PAS) and other cytosolic punctate compartments. We show that Atg9 and Atg23 cycle through the PAS in a process governed by the Atg1-Atg13 signaling complex. Atg1 kinase activity is essential only for retrograde transport of Atg23, while recycling of Atg9 requires additional factors including Atg18 and Atg2. We postulate that Atg9 employs a recycling system mechanistically similar to that used at yeast early and late endosomes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Autophagy / physiology*
  • Autophagy-Related Proteins
  • Cell Compartmentation / physiology
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Endosomes / metabolism
  • Lysosomes / metabolism
  • Macromolecular Substances
  • Membrane Proteins / metabolism*
  • Models, Biological
  • Phagosomes / metabolism*
  • Phagosomes / ultrastructure
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoproteins / metabolism
  • Protein Kinases / metabolism
  • Protein Transport / physiology
  • Protein-Serine-Threonine Kinases / metabolism
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Transport Vesicles / metabolism*
  • Transport Vesicles / ultrastructure

Substances

  • ATG13 protein, S cerevisiae
  • ATG9 protein, S cerevisiae
  • Adaptor Proteins, Signal Transducing
  • Atg23 protein, S cerevisiae
  • Autophagy-Related Proteins
  • Macromolecular Substances
  • Membrane Proteins
  • Phosphoproteins
  • Saccharomyces cerevisiae Proteins
  • Protein Kinases
  • ATG1 protein, S cerevisiae
  • Phosphatidylinositol 3-Kinases
  • Protein-Serine-Threonine Kinases