Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages

Nat Cell Biol. 2009 Apr;11(4):385-96. doi: 10.1038/ncb1846. Epub 2009 Mar 8.

Abstract

Beclin 1, a protein essential for autophagy, binds to hVps34/Class III phosphatidylinositol-3-kinase and UVRAG. Here, we have identified two Beclin 1 associated proteins, Atg14L and Rubicon. Atg14L and UVRAG bind to Beclin 1 in a mutually exclusive manner, whereas Rubicon binds only to a subpopulation of UVRAG complexes; thus, three different Beclin 1 complexes exist. GFP-Atg14L localized to the isolation membrane and autophagosome, as well as to the ER and unknown puncta. Knockout of Atg14L in mouse ES cells caused a defect in autophagosome formation. GFP-Rubicon was localized at the endosome/lysosome. Knockdown of Rubicon caused enhancement of autophagy, especially at the maturation step, as well as enhancement of endocytic trafficking. These data suggest that the Beclin 1-hVps34 complex functions in two different steps of autophagy by altering the subunit composition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Vesicular Transport / metabolism*
  • Animals
  • Apoptosis Regulatory Proteins / metabolism*
  • Autophagy*
  • Beclin-1
  • Cell Line, Tumor
  • Endocytosis
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Membrane Proteins / metabolism*
  • Mice
  • Microtubule-Associated Proteins / metabolism
  • Multiprotein Complexes / metabolism
  • Phagosomes / ultrastructure
  • Protein Binding
  • Protein Processing, Post-Translational
  • RNA, Small Interfering / metabolism
  • Recombinant Fusion Proteins / metabolism

Substances

  • Adaptor Proteins, Vesicular Transport
  • Apoptosis Regulatory Proteins
  • BECN1 protein, human
  • Beclin-1
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Multiprotein Complexes
  • RNA, Small Interfering
  • Recombinant Fusion Proteins
  • light chain 3, human
  • Green Fluorescent Proteins