Differential requirement for ATG2A domains for localization to autophagic membranes and lipid droplets

FEBS Lett. 2017 Dec;591(23):3819-3830. doi: 10.1002/1873-3468.12901. Epub 2017 Nov 20.

Abstract

ATG2 is one of the autophagy-related (ATG) proteins essential for autophagosome formation and localizes to isolation membranes and lipid droplets in mammalian cells. Here, we investigated the requirement of regions in ATG2A for its organellar localization and function. The N-terminal amino acids 1-198 and the C-terminal amino acids 1830-1938 are required for the localization to isolation membranes and lipid droplets, respectively. The C-terminal region is not required for the localization to isolation membranes and for autophagy. We also identified an amphipathic helix in ATG2A that is required for both its localization to organelles and autophagosome formation. These data suggest that the dual localization of ATG2A is regulated by different regions.

Keywords: ATG2; VPS13; amphipathic helix; autophagy; lipid droplet.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Autophagosomes / metabolism
  • Autophagosomes / ultrastructure
  • Autophagy / physiology*
  • Autophagy-Related Proteins / chemistry
  • Autophagy-Related Proteins / genetics
  • Autophagy-Related Proteins / metabolism
  • Cells, Cultured
  • Gene Knockout Techniques
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Lipid Droplets / metabolism
  • Lipid Droplets / ultrastructure
  • Membrane Proteins / chemistry*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Protein Domains
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Vesicular Transport Proteins / chemistry
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / metabolism

Substances

  • ATG2A protein, human
  • ATG2B protein, human
  • Autophagy-Related Proteins
  • Membrane Proteins
  • Recombinant Proteins
  • Vesicular Transport Proteins

Associated data

  • GENBANK/NP_055919